Challenging and emerging pathogens in cystic fibrosis

Vrankrijker, A.M.M. de; Wolfs, Tom F. W.; Ent, Cornelis K. van der

doi:10.1016/j.prrv.2010.07.003

Cited by 68 publications

(49 citation statements)

References 106 publications

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“…Culture-dependent analysis of CF airway infection reveals that Pseudomonas aeruginosa is the dominant bacterial pathogen in most adults with CF [2]. However, the recent application of culture-independent molecular techniques, based on the sequencing of the gene encoding bacterial 16S rRNA, have revealed a complex microbiome in the CF airway [3][4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Pyrosequencing reveals transient cystic fibrosis lung microbiome changes with intravenous antibiotics

et al. 2014

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Chronic airway infection in adults with cystic fibrosis (CF) is polymicrobial and the impact of intravenous antibiotics on the bacterial community composition is poorly understood. We employed culture-independent molecular techniques to explore the early effects of i.v. antibiotics on the CF airway microbiome.DNA was extracted from sputum samples collected from adult subjects with CF at three time-points (before starting treatment, and at day 3 and day 8-10 of i.v. antibiotics) during treatment of an infective pulmonary exacerbation. Microbial community profiles were derived through analysis of bacterial-derived 16S ribosomal RNA by pyrosequencing and changes over time were compared. 59 sputum samples were collected during 24 pulmonary exacerbations from 23 subjects. Between treatment onset and day 3 there was a significant reduction in the relative abundance of Pseudomonas and increased microbial diversity. By day 8-10, bacterial community composition was similar to pre-treatment. Changes in community composition did not predict improvements in lung function.The relative abundance of Pseudomonas falls rapidly in subjects with CF receiving i.v. antibiotic treatment for a pulmonary exacerbation and is accompanied by an increase in overall microbial diversity. However, this effect is not maintained beyond the first week of treatment. @ERSpublications Changes in the CF microbiome in response to i.v. antibiotics are not sustained despite ongoing antibiotic pressure

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Section: Introductionmentioning

confidence: 99%

Pyrosequencing reveals transient cystic fibrosis lung microbiome changes with intravenous antibiotics

et al. 2014

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“…The airways of patients are predominantly infected by specific pathogens, both Staphylococcus aureus and Pseudomonas aeruginosa are frequently identified and are often associated with significant inflammation and lung damage [2].…”

Section: Introductionmentioning

confidence: 99%

Haemophilus influenzae and Haemophilus parainfluenza in Cystic Fibrosis: 15 Years Experience

Ebbing¹,

Robertson

Robinson

2015

J Medical Microbiol Diagnosis

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“…seudomonas aeruginosa is a common nosocomial pathogen (1) and a major cause of morbidity and mortality in patients with cystic fibrosis (CF) (2,3). Treatment of P. aeruginosa infections is complicated by the organism's innate resistance to many antimicrobials, a product of its impressive intrinsic resistome (4) and its access to an array of acquired resistance mechanisms (5,6), with difficult-to-treat multidrug-resistant (MDR) (7) and extremely drug-resistant (8, 9) P. aeruginosa organisms becoming increasingly common.…”

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confidence: 99%

Potentiation of Aminoglycoside Activity in Pseudomonas aeruginosa by Targeting the AmgRS Envelope Stress-Responsive Two-Component System

Poole

Gilmour

Farha

et al. 2016

Antimicrob Agents Chemother

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A screen for agents that potentiated the activity of paromomycin (PAR), a 4,5-linked aminoglycoside (AG), against wild-type Pseudomonas aeruginosa identified the RNA polymerase inhibitor rifampin (RIF). RIF potentiated additional 4,5-linked AGs, such as neomycin and ribostamycin, but not the clinically important 4,6-linked AGs amikacin and gentamicin. Potentiation was absent in a mutant lacking the AmgRS envelope stress response two-component system (TCS), which protects the organism from AG-generated membrane-damaging aberrant polypeptides and, thus, promotes AG resistance, an indication that RIF was acting via this TCS in potentiating 4,5-linked AG activity. Potentiation was also absent in a RIF-resistant RNA polymerase mutant, consistent with its potentiation of AG activity being dependent on RNA polymerase perturbation. PAR-inducible expression of the AmgRS-dependent genes htpX and yccA was reduced by RIF, suggesting that AG activation of this TCS was compromised by this agent. Still, RIF did not compromise the membrane-protective activity of AmgRS, an indication that it impacted some other function of this TCS. RIF potentiated the activities of 4,5-linked AGs against several AG-resistant clinical isolates, in two cases also potentiating the activity of the 4,6-linked AGs. These cases were, in one instance, explained by an observed AmgRS-dependent expression of the MexXY multidrug efflux system, which accommodates a range of AGs, with RIF targeting of AmgRS undermining mexXY expression and its promotion of resistance to 4,5-and 4,6-linked AGs. Given this link between AmgRS, MexXY expression, and pan-AG resistance in P. aeruginosa, RIF might be a useful adjuvant in the AG treatment of P. aeruginosa infections. P seudomonas aeruginosa is a common nosocomial pathogen (1) and a major cause of morbidity and mortality in patients with cystic fibrosis (CF) (2, 3). Treatment of P. aeruginosa infections is complicated by the organism's innate resistance to many antimicrobials, a product of its impressive intrinsic resistome (4) and its access to an array of acquired resistance mechanisms (5, 6), with difficult-to-treat multidrug-resistant (MDR) (7) and extremely drug-resistant (8, 9) P. aeruginosa organisms becoming increasingly common. In the face of this intrinsic and acquired multidrug resistance, the use of agents historically used less commonly owing to issues of toxicity (e.g., the polymyxins) (10, 11) and the use of drug combination therapy (12, 13) are increasingly promoted. Still, despite much in vitro evidence for synergistic drug combinations being effective against MDR P. aeruginosa (14-20), the clinical benefits of drug combinations are less obvious (13,21,22).Aminoglycosides (AGs) have a long history in the management of P. aeruginosa infections, particularly in the case of lung infections in patients with cystic fibrosis (23,24), and are often used in combination with ␤-lactams (25-27) owing to a well-established synergy between these two antimicrobial classes (18,20,(26)(27)(28)(29). ␤-Lactam synergy ...

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Challenging and emerging pathogens in cystic fibrosis

Cited by 68 publications

References 106 publications

Pyrosequencing reveals transient cystic fibrosis lung microbiome changes with intravenous antibiotics

Pyrosequencing reveals transient cystic fibrosis lung microbiome changes with intravenous antibiotics

Haemophilus influenzae and Haemophilus parainfluenza in Cystic Fibrosis: 15 Years Experience

Potentiation of Aminoglycoside Activity in Pseudomonas aeruginosa by Targeting the AmgRS Envelope Stress-Responsive Two-Component System

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