RARE DISEASE
Pneumonia caused by Pseudomonas aeruginosa infection
Pneumonia caused by Pseudomonas aeruginosa infection
Pneumonia caused by Pseudomonas aeruginosa infection
Drug discovery
8
drugs
With orphan designations
Overview
Pseudomonas aeruginosa pneumonia is a severe infection primarily associated with healthcare settings, particularly ventilator-associated pneumonia (VAP) in ICU patients. It accounts for ~20% of ICU-acquired pneumonias and carries high mortality (28–42.8%) due to intrinsic antibiotic resistance and frequent multidrug-resistant (MDR) strains. Community-acquired cases are rare (0.9–4.2%) but linked to chronic lung diseases like COPD or bronchiectasis [1][2][4][6][12].
Population
High-risk groups: ICU patients on mechanical ventilation, immunosuppressed individuals (neutropenia, cystic fibrosis), and those with structural lung disease (COPD, bronchiectasis) [1][6][12][16].
Prior P. aeruginosa colonization, recent hospitalization, or antibiotic use increases susceptibility [4][12][19].
Burden
Mortality: 30-day mortality reaches 28% in CAP and 42.8% in VAP; MDR strains increase mortality risk [2][12][17].
Economic impact: Hospital-acquired cases incur €19,000+ additional costs due to prolonged ICU stays [9].
Antibiotic resistance: MDR strains cause 33% of VAP cases globally, with resistance rates exceeding 80% in high-risk regions [12][14].
Therapies
Empirical therapy: Novel β-lactam/β-lactamase inhibitors (ceftolozane-tazobactam, ceftazidime-avibactam) or cefiderocol for suspected MDR strains [3][8][13].
Definitive therapy: Guided by susceptibility testing; avoid unnecessary antipseudomonal drugs in low-risk CAP cases to reduce resistance [2][3][13].
Adjunctive approaches: Investigational therapies (phages, vaccines) for refractory MDR/XDR infections [8][14].
Categories: rare respiratory diseases
Research Papers
924 drug discovery papers about Pneumonia caused by Pseudomonas aeruginosa infection, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
924 drug discovery papers about Pneumonia caused by Pseudomonas aeruginosa infection, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-14 | Real-World Data on the Effectiveness and Use of Intravenous Fosfomycin for the Treatment of Difficult-to-Treat Infections Caused by Carbapenem-Resistant Gram-Negative Bacteria-A Subgroup Analysis from the FORTRESS Study.
This subgroup analysis of the FORTRESS study aimed to evaluate clinical and microbiological outcomes, treatment patterns, and safety of intravenous fosfomycin (FOS)-containing regimens for the treatment of infections due to carbapenem-resistant (CR) Gram-negative bacteria in a real-world setting. Interim data from patients treated with FOS for infections due to CR pathogens were analyzed from the ongoing prospective, multicenter, multinational, observational FORTRESS study. Key outcomes included patient demographics, clinical and infection characteristics at baseline, treatment patterns, and indications of FOS use, as well as clinical, microbiological, and safety outcomes. Exploratory Firth univariate and multivariate logistic regression were performed to identify factors associated with successful clinical response. The subgroup included 161 patients (median age 60 years, 30.4% female, median APACHE II score 15), of whom 59.6% required intensive care, and 41.6% had sepsis at baseline. The most common indications for FOS therapy were hospital-acquired/ventilator-associated pneumonia (28.0%), bacteremia/sepsis (26.1%), and complicated urinary tract infections (24.8%). Infections were predominantly caused by Klebsiella pneumoniae (62.7%), Pseudomonas aeruginosa (28.6%), and Acinetobacter baumannii (17.4%). Carbapenem resistance was mainly mediated by Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-β-lactamase (NDM). In the majority of patients, FOS was part of a combination regimen (91.3%), with ceftazidime-avibactam being the most frequently used partner antibiotic. Overall, clinical success was achieved in 79.4% of patients, while the successful clinical response and microbiological cure rates were 87.5% and 81.3% at the end of FOS treatment, respectively. All-cause in-hospital mortality was 9.9%. Electrolyte imbalances were the most commonly reported adverse drug reactions, but they were mostly not treatment-limiting. The real-world data of this subgroup analysis suggest that FOS-containing regimens were associated with generally favorable clinical and microbiological outcomes and acceptable tolerability in patients with severe infections due to CR Gram-negative bacteria.
2026-08-11 | Mitophagy IncreasesResistance against Infection of Pseudomonas aeruginosa through the PHB2 / PARL / PGAM5 / PINK1 Axis
Abstract Pseudomonas aeruginosa (P.a) is a common opportunistic pathogen causing serious infection and complications in diverse populations, especially under immunodeficient conditions. Previous studies indicate that mitophagy activation is related to multiple conditions and processes in the human body, including infectious diseases. It has been recently implicated that the PARL-PGAM5-PINK1 axis activates mitophagy, but its regulatory role in pneumonia is unclear. We hypothesize that mitophagy receptor PHB2 orchestrates an autophagic process through PARL and PGAM5 to limit P.a. infection and inflammation. By knocking down PHB2, we explored the regulatory role of mitophagy in P.a infection and evaluated the underlying mechanism of the PARL-PGAM5-PINK1 signals both in vitro and in P.a pneumonia mice. Our study also reveals that the critical factors, such as PARL and PINK1, may have potential for therapeutic targeting during Pseudomonas infection.
2026-08-06 | Genomic diversity of Pseudomonas aeruginosa causing bacteremic pneumonia in an intensive care unit, with emergence of an OXA-796-producing NDM-1 ST773 isolate
Pseudomonas aeruginosa bacteremic pneumonia carries exceptionally high mortality, yet there is a paucity of genomic characterization of the strains causing this infection. We performed hybrid sequencing (Illumina and Oxford Nanopore) of 12 non-redundant P. aeruginosa isolates from patients with severe bacteremic pneumonia admitted to the intensive care unit of a tertiary hospital between 2015 and 2023. The 12 isolates were assigned to nine distinct sequence types, suggesting that severe bacteremic pneumonia can arise from diverse P. aeruginosa lineages rather than being dominated by a single specialized or high-risk clone. In the combined dataset of our isolates and publicly available Korean P. aeruginosa genomes, type III secretion system exotoxin genotypes exoU and exoS showed a mutually exclusive and phylogenetically segregated distribution, as previously reported, with both genotypes represented among bacteremic pneumonia isolates. Carbapenemase genes were detected in only one isolate, PA22 (ST773), which harboured bla NDM-1 together with bla OXA-796 and was the only isolate displaying phenotypic carbapenem resistance and multidrug resistance. To assess the clonal relationship between bla NDM-1 -positive PA22 and the carbapenemase-negative ST773 isolate PA20 and to track the evolution of PA22 resistome within a broader epidemiological context, we investigated the population structure of a global ST773 dataset. Core genome MLST-based minimum spanning trees revealed a deep bifurcation within ST773, separating bla NDM-1 -positive and carbapenemase-negative lineages. Korean ST773 isolates formed two distinct clusters within the NDM-1-positive lineage, with the PA22-containing cluster phylogenetically proximal to isolates from the United States. Within the NDM-1-positive Korean cluster, bla OXA-796 was located in conserved class 1 integron gene cassette arrays that exhibit ongoing structural diversification among closely related isolates, evidenced by variable integration of IS110 elements. Our findings demonstrate that severe bacteremic pneumonia arises from phylogenetically diverse P. aeruginosa lineages and provide genomic context for the NDM-1-producing ST773 clone that is rapidly emerging in Korea.
2026-07-22 | Multifaceted effects of galU deletion on phenotype and virulence of Pseudomonas aeruginosa in vitro and in vivo
Pseudomonas aeruginosa is a widespread Gram-negative opportunistic pathogen in environmental and hospital settings, frequently causing respiratory diseases such as cystic fibrosis (CF), chronic obstructive pulmonary disorder (COPD) and ventilator-associated pneumonia. In our previous study, a galU-deleted clinical P. aeruginosa was found to exhibit increased susceptibility to polymyxins. The galU gene plays an important role in the biosynthesis of lipopolysaccharide (LPS) O-antigen. Here, we systematically evaluated the effects of galU deletion on the phenotype and virulence of P. aeruginosa PAO1. A galU deletion mutant was successfully constructed in P. aeruginosa PAO1 by CRISPR/Cas9, and the complementation was accomplished by pUCP18 plasmid carrying wildtype galU. The changes in phenotype, virulence and pathogenicity were systemically studied. The results revealed that knockout of galU led to the loss of O-antigen, which affected growth, virulence and pathogenicity through various ways in P. aeruginosa, and significantly affected the susceptibility of P. aeruginosa to polymyxins. Mechanism study suggested the involvements of quorum sensing, Entner-Doudoroff pathway and tyrosine metabolism, etc on bacterial virulence, antibiotic susceptibility changes after galU deletion. galU and the related pathways may serve as effective targets for treatment of P. aeruginosa infection, providing a theoretical basis for the development of novel antibacterial drugs.
2026-06-27 | Inhalable bacteriophage endolysins: a novel therapeutic strategy for drug-resistant bacterial pulmonary infections - a comprehensive review.
Pulmonary infections caused by multidrug-resistant (MDR) bacteria pose a severe global health threat with high mortality rates, especially in hospital-acquired pneumonia. The stagnation of new antibiotic development underscores the urgent need for alternative therapeutics. This review summarizes recent advances in the application of bacteriophage endolysins against major MDR respiratory pathogens, including Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. We focus on their mechanisms of action, synergistic effects with antibiotics, and efficacy against biofilms. Endolysins demonstrate potent and species-specific lytic activity against a broad spectrum of MDR bacteria. A key advantage is their low propensity for inducing resistance. Critically, when administered via optimized inhalation delivery systems, endolysins can achieve high local concentrations in the lungs - though this depends on factors such as the aerosol device, formulation properties and patient-related variables - effectively eradicating pathogens in animal models of pneumonia with minimal systemic toxicity. This direct pulmonary delivery approach bypasses many challenges associated with systemic administration and enhances therapeutic outcomes. Endolysins represent a promising paradigm shift in combating drug-resistant bacterial pulmonary infections. Their rapid lytic activity, synergy with conventional antibiotics, and suitability for inhalable formulation position them as a potent adjunct or alternative therapy. While challenges in stabilization and large-scale production remain, advancing inhalation delivery systems for endolysins holds immense potential to holds immense potential to revolutionize the treatment of recalcitrant respiratory infections.
2026-08-14 | Real-World Data on the Effectiveness and Use of Intravenous Fosfomycin for the Treatment of Difficult-to-Treat Infections Caused by Carbapenem-Resistant Gram-Negative Bacteria-A Subgroup Analysis from the FORTRESS Study.
This subgroup analysis of the FORTRESS study aimed to evaluate clinical and microbiological outcomes, treatment patterns, and safety of intravenous fosfomycin (FOS)-containing regimens for the treatment of infections due to carbapenem-resistant (CR) Gram-negative bacteria in a real-world setting. Interim data from patients treated with FOS for infections due to CR pathogens were analyzed from the ongoing prospective, multicenter, multinational, observational FORTRESS study. Key outcomes included patient demographics, clinical and infection characteristics at baseline, treatment patterns, and indications of FOS use, as well as clinical, microbiological, and safety outcomes. Exploratory Firth univariate and multivariate logistic regression were performed to identify factors associated with successful clinical response. The subgroup included 161 patients (median age 60 years, 30.4% female, median APACHE II score 15), of whom 59.6% required intensive care, and 41.6% had sepsis at baseline. The most common indications for FOS therapy were hospital-acquired/ventilator-associated pneumonia (28.0%), bacteremia/sepsis (26.1%), and complicated urinary tract infections (24.8%). Infections were predominantly caused by Klebsiella pneumoniae (62.7%), Pseudomonas aeruginosa (28.6%), and Acinetobacter baumannii (17.4%). Carbapenem resistance was mainly mediated by Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-β-lactamase (NDM). In the majority of patients, FOS was part of a combination regimen (91.3%), with ceftazidime-avibactam being the most frequently used partner antibiotic. Overall, clinical success was achieved in 79.4% of patients, while the successful clinical response and microbiological cure rates were 87.5% and 81.3% at the end of FOS treatment, respectively. All-cause in-hospital mortality was 9.9%. Electrolyte imbalances were the most commonly reported adverse drug reactions, but they were mostly not treatment-limiting. The real-world data of this subgroup analysis suggest that FOS-containing regimens were associated with generally favorable clinical and microbiological outcomes and acceptable tolerability in patients with severe infections due to CR Gram-negative bacteria.
2026-08-11 | Mitophagy IncreasesResistance against Infection of Pseudomonas aeruginosa through the PHB2 / PARL / PGAM5 / PINK1 Axis
Abstract Pseudomonas aeruginosa (P.a) is a common opportunistic pathogen causing serious infection and complications in diverse populations, especially under immunodeficient conditions. Previous studies indicate that mitophagy activation is related to multiple conditions and processes in the human body, including infectious diseases. It has been recently implicated that the PARL-PGAM5-PINK1 axis activates mitophagy, but its regulatory role in pneumonia is unclear. We hypothesize that mitophagy receptor PHB2 orchestrates an autophagic process through PARL and PGAM5 to limit P.a. infection and inflammation. By knocking down PHB2, we explored the regulatory role of mitophagy in P.a infection and evaluated the underlying mechanism of the PARL-PGAM5-PINK1 signals both in vitro and in P.a pneumonia mice. Our study also reveals that the critical factors, such as PARL and PINK1, may have potential for therapeutic targeting during Pseudomonas infection.
2026-08-06 | Genomic diversity of Pseudomonas aeruginosa causing bacteremic pneumonia in an intensive care unit, with emergence of an OXA-796-producing NDM-1 ST773 isolate
Pseudomonas aeruginosa bacteremic pneumonia carries exceptionally high mortality, yet there is a paucity of genomic characterization of the strains causing this infection. We performed hybrid sequencing (Illumina and Oxford Nanopore) of 12 non-redundant P. aeruginosa isolates from patients with severe bacteremic pneumonia admitted to the intensive care unit of a tertiary hospital between 2015 and 2023. The 12 isolates were assigned to nine distinct sequence types, suggesting that severe bacteremic pneumonia can arise from diverse P. aeruginosa lineages rather than being dominated by a single specialized or high-risk clone. In the combined dataset of our isolates and publicly available Korean P. aeruginosa genomes, type III secretion system exotoxin genotypes exoU and exoS showed a mutually exclusive and phylogenetically segregated distribution, as previously reported, with both genotypes represented among bacteremic pneumonia isolates. Carbapenemase genes were detected in only one isolate, PA22 (ST773), which harboured bla NDM-1 together with bla OXA-796 and was the only isolate displaying phenotypic carbapenem resistance and multidrug resistance. To assess the clonal relationship between bla NDM-1 -positive PA22 and the carbapenemase-negative ST773 isolate PA20 and to track the evolution of PA22 resistome within a broader epidemiological context, we investigated the population structure of a global ST773 dataset. Core genome MLST-based minimum spanning trees revealed a deep bifurcation within ST773, separating bla NDM-1 -positive and carbapenemase-negative lineages. Korean ST773 isolates formed two distinct clusters within the NDM-1-positive lineage, with the PA22-containing cluster phylogenetically proximal to isolates from the United States. Within the NDM-1-positive Korean cluster, bla OXA-796 was located in conserved class 1 integron gene cassette arrays that exhibit ongoing structural diversification among closely related isolates, evidenced by variable integration of IS110 elements. Our findings demonstrate that severe bacteremic pneumonia arises from phylogenetically diverse P. aeruginosa lineages and provide genomic context for the NDM-1-producing ST773 clone that is rapidly emerging in Korea.
2026-07-22 | Multifaceted effects of galU deletion on phenotype and virulence of Pseudomonas aeruginosa in vitro and in vivo
Pseudomonas aeruginosa is a widespread Gram-negative opportunistic pathogen in environmental and hospital settings, frequently causing respiratory diseases such as cystic fibrosis (CF), chronic obstructive pulmonary disorder (COPD) and ventilator-associated pneumonia. In our previous study, a galU-deleted clinical P. aeruginosa was found to exhibit increased susceptibility to polymyxins. The galU gene plays an important role in the biosynthesis of lipopolysaccharide (LPS) O-antigen. Here, we systematically evaluated the effects of galU deletion on the phenotype and virulence of P. aeruginosa PAO1. A galU deletion mutant was successfully constructed in P. aeruginosa PAO1 by CRISPR/Cas9, and the complementation was accomplished by pUCP18 plasmid carrying wildtype galU. The changes in phenotype, virulence and pathogenicity were systemically studied. The results revealed that knockout of galU led to the loss of O-antigen, which affected growth, virulence and pathogenicity through various ways in P. aeruginosa, and significantly affected the susceptibility of P. aeruginosa to polymyxins. Mechanism study suggested the involvements of quorum sensing, Entner-Doudoroff pathway and tyrosine metabolism, etc on bacterial virulence, antibiotic susceptibility changes after galU deletion. galU and the related pathways may serve as effective targets for treatment of P. aeruginosa infection, providing a theoretical basis for the development of novel antibacterial drugs.
2026-06-27 | Inhalable bacteriophage endolysins: a novel therapeutic strategy for drug-resistant bacterial pulmonary infections - a comprehensive review.
Pulmonary infections caused by multidrug-resistant (MDR) bacteria pose a severe global health threat with high mortality rates, especially in hospital-acquired pneumonia. The stagnation of new antibiotic development underscores the urgent need for alternative therapeutics. This review summarizes recent advances in the application of bacteriophage endolysins against major MDR respiratory pathogens, including Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. We focus on their mechanisms of action, synergistic effects with antibiotics, and efficacy against biofilms. Endolysins demonstrate potent and species-specific lytic activity against a broad spectrum of MDR bacteria. A key advantage is their low propensity for inducing resistance. Critically, when administered via optimized inhalation delivery systems, endolysins can achieve high local concentrations in the lungs - though this depends on factors such as the aerosol device, formulation properties and patient-related variables - effectively eradicating pathogens in animal models of pneumonia with minimal systemic toxicity. This direct pulmonary delivery approach bypasses many challenges associated with systemic administration and enhances therapeutic outcomes. Endolysins represent a promising paradigm shift in combating drug-resistant bacterial pulmonary infections. Their rapid lytic activity, synergy with conventional antibiotics, and suitability for inhalable formulation position them as a potent adjunct or alternative therapy. While challenges in stabilization and large-scale production remain, advancing inhalation delivery systems for endolysins holds immense potential to holds immense potential to revolutionize the treatment of recalcitrant respiratory infections.
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Drug Discovery Landscape
8 orphan drug designations for Pneumonia caused by Pseudomonas aeruginosa infection.
8 orphan drug designations for Pneumonia caused by Pseudomonas aeruginosa infection.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Human monoclonal antibody IgM directed against Pseudomonas aeruginosa serotype O1 O-polysaccharide [KBPA 104] | antibodies | EMA | 2010-01-28 | — | Envestia Limited |
human monoclonal antibody directed against serotype O1 Pseudomonas aeruginosa | antibodies | FDA | 2010-01-06 | — | Kenta Biotech Limited |
Tobramycin [Vantobra] | small molecules | EMA | 2009-02-27 | — | Pari Pharma GmbH |
Human monoclonal antibody directed against serotype 011 Pseudomonas aeruginosa | antibodies | FDA | 2006-09-18 | — | Kenta Biotech Limited |
Human monoclonal antibody against Pseudomonas aeruginosa serotype O11 | antibodies | EMA | 2006-06-29 | — | Marcello Menapace |
Tobramycin [Fluidosomes Tobramycin] | small molecules | EMA | 2006-04-11 | — | [INACTIVE] Axentis Phama Limited |
Tobramycin [Tobi Podhaler] | small molecules | EMA | 2003-03-17 | — | Viatris Healthcare Limited |
Pseudomonas aeruginosa octavalent conjugated vaccine [Aerugen] | vaccines | EMA | 2001-12-11 | — | Recordati Rare Diseases |
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