scholarly journals Pseudomonas aeruginosa and Klebsiella pneumoniae Adaptation to Innate Immune Clearance Mechanisms in the Lung

2018 ◽  
Vol 10 (5-6) ◽  
pp. 442-454 ◽  
Author(s):  
Sebastian A. Riquelme ◽  
Danielle Ahn ◽  
Alice Prince

Many different species of gram-negative bacteria are associated with infection in the lung, causing exacerbations of chronic obstructive pulmonary disease, cystic fibrosis (CF), and ventilator-associated pneumonias. These airway pathogens must adapt to common host clearance mechanisms that include killing by antimicrobial peptides, antibiotics, oxidative stress, and phagocytosis by leukocytes. Bacterial adaptation to the host is often evident phenotypically, with increased extracellular polysaccharide production characteristic of some biofilm-associated organisms. Given the relatively limited repertoire of bacterial strategies to elude airway defenses, it seems likely that organisms sharing the same ecological niche might also share common strategies to persistently infect the lung. In this review, we will highlight some of the major factors responsible for the adaptation of Pseudomonas aeruginosa to the lung, addressing how growth in biofilms enables persistent infection, relevant to, but not limited to, the pathogenesis of infection in CF. In contrast, we will discuss how carbapenem-resistant Klebsiella pneumoniae evade immune clearance, an organism often associated with ventilator-associated pneumonia and health-care-acquired pneumonias, but not a typical pathogen in CF.


Author(s):  
Rushuang Yan ◽  
Ye Lu ◽  
Yiwei Zhu ◽  
Peng Lan ◽  
Shengnan Jiang ◽  
...  

Hypervirulent Klebsiella pneumoniae strains are typically associated with severe infections and susceptible to most antimicrobial agents. In 2017, a carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) strain was isolated from the sputum of a chronic obstructive pulmonary disease (COPD) patient in Zhejiang, China. The goal of the present study was to characterize the molecular features of the CR-hvKP isolate ZJ27003 and its blaKPC-2-harboring plasmid p27003_KPC. Antimicrobial susceptibility was evaluated using the broth microdilution and agar dilution methods. String tests, serum-killing and mouse survival assays were performed to assess virulence, and plasmid conjugation was performed by filter mating. The complete genome sequence of ZJ27003 was acquired using a hybrid assembly of Illumina and Nanopore platform data. The sequence type (ST) of this CR-hvKP isolate was identified as ST23, which exhibits hypervirulence with high serum resistance and murine infection model. The strain is also resistant to carbapenems (imipenem, meropenem and ertapenem), aztreonam and cephalosporins. Additionally, the CR-hvKP isolate carries a 36,708-bp blaKPC-2-harboring plasmid, named p27003_KPC, belonging to the P1 incompatibility (Inc) group. The backbone of p27003_KPC is similar to that of a blaGES-5-harboring Pseudomonas aeruginosa plasmid, in which the blaGES-5 and its surrounding regions were replaced by a blaKPC-2-containing translocatable unit derived from Enterobacteriaceae. The results of a conjugation assay revealed that p27003_KPC can be transferred from K. pneumoniae to P. aeruginosa PAO1 and make the recipient resistant against carbapenem. The identification of a carbapenem-resistant hypervirulent K. pneumoniae isolate carrying and disseminating the blaKPC-2 gene highlights a severe threat to public health.



2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S88-S88
Author(s):  
Samuel Simon ◽  
Rosanna Li ◽  
Yu Shia Lin ◽  
Suri Mayer ◽  
Edward Chapnick ◽  
...  

Abstract Background Carbapenem-resistant gram-negative organisms are a continuously mounting threat, underscoring the need for effective antimicrobial stewardship interventions to improve the use of carbapenems. We sought to implement several multidisciplinary antimicrobial stewardship interventions beginning in January 2019 in an effort to reduce unnecessary meropenem use and the incidence of carbapenem-resistant gram-negatives. Methods Prospective audit and feedback was utilized daily in combination with weekly stewardship rounds between an Infectious Diseases pharmacist and physician in the Intensive Care Units. A second Infectious Diseases physician attended weekly interdisciplinary rounds on meropenem high-use units. Meropenem Days of Therapy (DOT) per 1,000 patient days and the incidence of meropenem resistant Pseudomonas aeruginosa and Klebsiella pneumoniae were compared by the chi-square test of proportions. Results Between 2018 and 2019 the institution’s meropenem DOT per 1,000 patient days decreased 33%, from 57 to 38 days per 1,000 patient days (difference, 19 days per 1,000 patient days; p< 0.001). In the hospital antibiogram, the meropenem susceptibility of Pseudomonas aeruginosa over the same time period increased from 71% to 77% of isolates (difference, 6%; p = 0.009). A non-significant decrease in the susceptibility of meropenem to Klebsiella pneumoniae was also observed from 92 to 90% (difference, 2%: p = 0.1658). Conclusion These data support the need for antimicrobial stewardship efforts targeting broad-spectrum antimicrobials such as meropenem. In the setting of a sustained decrease in meropenem use over 12 months, we observed a significant improvement in the percent susceptibility rate of Pseudomonas aeruginosa to meropenem for the first time in five years. Disclosures All Authors: No reported disclosures



Author(s):  
Parag Sharma

ABSTRACTBronchiectasis is a type of chronic obstructive pulmonary disease, defined as permanent abnormal dilation of bronchi due to vicious cycle of transmuralinfection and inflammation. Bronchiectasis is generally characterized by cough, wheeze, and dyspnea. Pathogens responsible for bronchiectasisinclude pathogens Haemophilus influenzae, Pseudomonas aeruginosa, Streptococcus pneumoniae, Staphylococcus aureus, and nontuberculousmycobacteria. Empirical antibiotic therapy and other drugs are used empirically in the management of bronchiectasis.Here, we discuss a case ofinfectious exacerbation of bronchiectasis successfully treated with an empirical use of ceftriaxone/sulbactam/disodium edetate-1034.Keywords: Bronchiectasis, Elores™, Ceftriaxone/sulbactam/disodium edetate-1034, Disodium edetate, Antibiotic resistance.



2021 ◽  
Vol 12 ◽  
Author(s):  
Jomkuan Theprungsirikul ◽  
Sladjana Skopelja-Gardner ◽  
Ashley S. Burns ◽  
Rachel M. Wierzbicki ◽  
William F. C. Rigby

Chronic Pseudomonas aeruginosa infection mysteriously occurs in the airways of patients with cystic fibrosis (CF), bronchiectasis (BE), and chronic obstructive pulmonary disease (COPD) in the absence of neutrophil dysfunction or neutropenia and is strongly associated with autoimmunity to bactericidal permeability-increasing protein (BPI). Here, we define a critical role for BPI in in vivo immunity against P. aeruginosa. Wild type and BPI-deficient (Bpi-/-) mice were infected with P. aeruginosa, and bacterial clearance, cell infiltrates, cytokine production, and in vivo phagocytosis were quantified. Bpi-/- mice exhibited a decreased ability to clear P. aeruginosa in vivo in concert with increased neutrophil counts and cytokine release. Bpi-/- neutrophils displayed decreased phagocytosis that was corrected by exogenous BPI in vitro. Exogenous BPI also enhanced clearance of P. aeruginosa in Bpi-/- mice in vivo by increasing P. aeruginosa uptake by neutrophils in a CD18-dependent manner. These data indicate that BPI plays an essential role in innate immunity against P. aeruginosa through its opsonic activity and suggest that perturbations in BPI levels or function may contribute to chronic lung infection with P. aeruginosa.





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