Long-term use of tube feeding in children with cystic fibrosis: results from two Belgian CF centers

AbstractPseudomonas aeruginosa uses quorum sensing (QS) to modulate the expression of several virulence factors that enable it to establish severe infections. The QS system in P. aeruginosa is complex, intricate and is dominated by two main N-acyl-homoserine lactone circuits, LasRI and RhlRI. These two QS systems work in a hierarchical fashion with LasRI at the top, directly regulating RhlRI. Together these QS circuits regulate several virulence associated genes, metabolites, and enzymes in P. aeruginosa. Paradoxically, LasR mutants are frequently isolated from chronic P. aeruginosa infections, typically among cystic fibrosis (CF) patients. This suggests P. aeruginosa can undergo significant evolutionary pathoadaptation to persist in long term chronic infections. In contrast, mutations in the RhlRI system are less common. Here, we have isolated a clinical strain of P. aeruginosa from a CF patient that has deleted the transcriptional regulator RhlR entirely. Whole genome sequencing shows the rhlR locus is deleted in PA80 alongside a few non-synonymous mutations in virulence factors including protease lasA and rhamnolipid rhlA, rhlB, rhlC. Importantly we did not observe any mutations in the LasRI QS system. PA80 does not appear to have an accumulation of mutations typically associated with several hallmark pathoadaptive genes (i.e., mexT, mucA, algR, rpoN, exsS, ampR). Whole genome comparisons show that P. aeruginosa strain PA80 is closely related to the hypervirulent Liverpool epidemic strain (LES) LESB58. PA80 also contains several genomic islands (GI’s) encoding virulence and/or resistance determinants homologous to LESB58. To further understand the effect of these mutations in PA80 QS regulatory and virulence associated genes, we compared transcriptional expression of genes and phenotypic effects with isogenic mutants in the genetic reference strain PAO1. In PAO1, we show that deletion of rhlR has a much more significant impact on the expression of a wide range of virulence associated factors rather than deletion of lasR. In PA80, no QS regulatory genes were expressed, which we attribute to the inactivation of the RhlRI QS system by deletion of rhlR and mutation of rhlI. This study demonstrates that inactivation of the LasRI system does not impact RhlRI regulated virulence factors. PA80 has bypassed the common pathoadaptive mutations observed in LasR by targeting the RhlRI system. This suggests that RhlRI is a significant target for the long-term persistence of P. aeruginosa in chronic CF patients. This raises important questions in targeting QS systems for therapeutic interventions.

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Frailty and hospitalization-associated disability after pneumonia: A prospective cohort study

BMC Geriatrics ◽

10.1186/s12877-021-02049-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chan Mi Park ◽

Wonsock Kim ◽

Hye Chang Rhim ◽

Eun Sik Lee ◽

Jong Hun Kim ◽

...

Keyword(s):

Older Adults ◽

Primary Outcome ◽

Long Term Care ◽

Functional Decline ◽

Tube Feeding ◽

Term Care ◽

Pneumonia Severity ◽

Frailty Assessment ◽

Nasogastric Tube Feeding

Abstract Background Pneumonia is a major cause of morbidity and mortality in older adults. The role of frailty assessment in older adults with pneumonia is not well defined. Our purpose of the study was to investigate 30-day clinical course and functional outcomes of pneumonia in older adults with different levels of frailty. Methods A prospective cohort was conducted at a university hospital in Seoul, Korea with 176 patients who were 65 years or older and hospitalized with pneumonia. A 50-item deficit-accumulation frailty index (FI) (range: 0–1; robust < 0.15, pre-frail 0.15–0.24, mild-to-moderately frail 0.25–0.44, and severely frail ≥ 0.45) and the pneumonia severity CURB-65 score (range: 0–5) were measured. Primary outcome was death or functional decline, defined as worsening dependencies in 21 daily activities and physical tasks in 30 days. Secondary outcomes were intensive care unit admission, psychoactive drug use, nasogastric tube feeding, prolonged hospitalization (length of stay > 15 days), and discharge to a long-term care institution. Results The population had a median age 79 (interquartile range, 75–84) years, 68 (38.6 %) female, and 45 (25.5 %) robust, 36 (47.4 %) pre-frail, 37 (21.0 %) mild-to-moderately frail, and 58 (33.0 %) severely frail patients. After adjusting for age, sex, and CURB-65, the risk of primary outcome for increasing frailty categories was 46.7 %, 61.1 %, 83.8 %, and 86.2 %, respectively (p = 0.014). The risk was higher in patients with frailty (FI ≥ 0.25) than without (FI < 0.25) among those with CURB-65 0–2 points (75 % vs. 52 %; p = 0.022) and among those with CURB-65 3–5 points (93 % vs. 65 %; p = 0.007). In addition, patients with greater frailty were more likely to require nasogastric tube feeding (robust vs. severe frailty: 13.9 % vs. 60.3 %) and prolonged hospitalization (18.2 % vs. 50.9 %) and discharge to a long-term care institution (4.4 % vs. 59.3 %) (p < 0.05 for all). Rates of intensive care unit admission and psychoactive drug use were similar. Conclusions Older adults with frailty experience high rates of death or functional decline in 30 days of pneumonia hospitalization, regardless of the pneumonia severity. These results underscore the importance of frailty assessment in the acute care setting.

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