Pseudomonas aeruginosa colonizes the airways of cystic fibrosis (CF) patients, causing infections that can last for decades. During the course of these infections, P. aeruginosa undergoes a number of ...genetic adaptations. One such adaptation is the loss of swimming motility functions. Another involves the formation of the rugose small colony variant (RSCV) phenotype, which is characterized by overproduction of the exopolysaccharides Pel and Psl. Here, we provide evidence that the two adaptations are linked. Using random transposon mutagenesis, we discovered that flagellar mutations are linked to the RSCV phenotype. We found that flagellar mutants overexpressed Pel and Psl in a surface-contact dependent manner. Genetic analyses revealed that flagellar mutants were selected for at high frequencies in biofilms, and that Pel and Psl expression provided the primary fitness benefit in this environment. Suppressor mutagenesis of flagellar RSCVs indicated that Psl overexpression required the mot genes, suggesting that the flagellum stator proteins function in a surface-dependent regulatory pathway for exopolysaccharide biosynthesis. Finally, we identified flagellar mutant RSCVs among CF isolates. The CF environment has long been known to select for flagellar mutants, with the classic interpretation being that the fitness benefit gained relates to an impairment of the host immune system to target a bacterium lacking a flagellum. Our new findings lead us to propose that exopolysaccharide production is a key gain-of-function phenotype that offers a new way to interpret the fitness benefits of these mutations.
Creating and maintaining a healthy work environment is part of the role of the perioperative nurse. Disruptive behavior negatively affects patient outcomes, nursing practice, and a facility's bottom ...line. If the disruptive behavior is not addressed, then the organization can be put at risk for legal action. The nurse must advocate for the patient by addressing disturbing behavior to ensure creation and maintenance of an environment that supports safe, quality care for the patient.
Opportunistic infections are often polymicrobial. Two of the most important bacterial opportunistic pathogens of humans, Pseudomonas aeruginosa and Staphylococcus aureus, frequently are coisolated ...from infections of catheters, endotracheal tubes, skin, eyes, and the respiratory tract, including the airways of people with cystic fibrosis (CF). Here, we show that suppression of S. aureus respiration by a P. aeruginosa exoproduct, 4-hydroxy-2-heptylquinoline-N-oxide (HQNO), protects S. aureus during coculture from killing by commonly used aminoglycoside antibiotics such as tobramycin. Furthermore, prolonged growth of S. aureus with either P. aeruginosa or with physiological concentrations of pure HQNO selects for typical S. aureus small-colony variants (SCVs), well known for stable aminoglycoside resistance and persistence in chronic infections, including those found in CF. We detected HQNO in the sputum of CF patients infected with P. aeruginosa, but not in uninfected patients, suggesting that this HQNO-mediated interspecies interaction occurs in CF airways. Thus, in all coinfections with P. aeruginosa, S. aureus may be underappreciated as a pathogen because of the formation of antibiotic-resistant and difficult to detect small-colony variants. Interspecies microbial interactions, analogous to those mediated by HQNO, commonly may alter not only the course of disease and the response to therapy, but also the population structure of bacterial communities that promote the health of host animals, plants, and ecosystems.
Despite recent advances in perioperative patient care, postsurgical pain continues to be undermanaged. There is increasing acceptance of the concept that effective postsurgical pain management is ...best achieved through combined use of more than one analgesic agent or technique, and overreliance on opioids produces unwanted side effects limiting their utility. Accordingly, a balanced, multimodal approach to pain management within the larger framework of an Enhanced Recovery After Surgery (ERAS) pathway has become standard at many institutions for perioperative care, to control postsurgical pain, reduce opioid-related adverse events, hasten postsurgical recovery, and shorten length of hospital stay. The success of ERAS is dependent on nurses and the multidisciplinary team to execute its standardized processes across the care continuum, including patient education, perioperative care, and postsurgical evaluation. Here, we review current concepts related to multimodal analgesia and ERAS regarding care of adult surgical patients and discuss the perioperative nurse's role within this paradigm.
Objective To assess the effects of Pseudomonas aeruginosa and Staphylococcus aureus infection on lower airway inflammation and clinical status in young children with cystic fibrosis (CF). Study ...design We studied 111 children age < 6 years who had 2 P aeruginosa –positive oropharyngeal cultures within 12 months. We examined bronchoalveolar lavage fluid (BALF) inflammatory markers (ie, cell count, differential, interleukin IL-8, IL-6, neutrophil elastase), CF-related bacterial pathogens, exotoxin A serology, and clinical indicators of disease severity. Results Young children with CF with both upper and lower airway P aeruginosa infection had higher neutrophil counts, higher IL-8 and free neutrophil elastase levels, increased likelihood of positive exotoxin A titers, and lower Shwachman scores compared with those with positive upper airway cultures only. S aureus was associated with increased lower airway inflammation, and the presence of both P aeruginosa and S aureus had an additive effect on concentrations of lower airway inflammatory markers. BALF markers of inflammation were increased with the number of different bacterial pathogens detected. Conclusions Young children with CF who have upper and lower airway P aeruginosa infection have increased endobronchial inflammation and poorer clinical status compared with those with only upper airway P aeruginosa infection. The independent and additive effects of S aureus on inflammation support the significance of polymicrobial infection in early CF lung disease.
Abstract Background Risk factors for initial Pseudomonas aeruginosa (Pa) acquisition, particularly environmental exposures, are poorly understood. We aimed to identify such risk factors in order to ...inform prevention strategies and identify high-risk populations. Methods The study cohort included all participants in the U.S. EPIC Observational Study who had no prior Pa-positive respiratory cultures (N = 889). Cox proportional hazard models were used to test the effects of factors on age at first Pa-positive respiratory culture. Results Cystic fibrosis (CF) genotype functional class had an important effect on age at initial Pa acquisition (hazard ratio (HR) comparing minimal to residual CFTR function 2.87 (95% CI 1.88, 4.39)). None of the modifiable risk factors evaluated, including cigarette smoke, hot tub use, breastfeeding, or daycare, was associated with age at Pa acquisition. Similarly, newborn screening was not associated with age at Pa acquisition (HR 0.85, 95% CI 0.66, 1.09). Key associations were validated in a CF Foundation National Patient Registry replication cohort. Conclusions Given the ubiquitous presence of Pa in the environment, it may be that many imposed lifestyle changes will have less impact on age at initial Pa acquisition than genetic determinants.
Adeno-associated virus (AAV) vectors are promising candidates for gene therapy directed to the lungs, in particular for treatment of cystic fibrosis (CF). In animal models of lung gene transfer, ...neutralizing antibodies in serum made in response to vector exposure have been associated with a partial to complete block to repeat transduction by vectors with the same capsid type, thus transduction by AAV vectors might be inefficient in humans previously exposed to the same AAV type. AAV type 2 (AAV2) has been used in clinical trials of lung gene transfer, but AAV5 and AAV6 have been shown to mediate more efficient transduction in rodent lungs and in cultured human airway epithelia compared with that of AAV2. Here we have measured neutralizing antibodies against AAV type 2, 5, and 6 vectors in serum from children and adults with CF, and from normal adults. About 30% of adults were seropositive for AAV2, 20-30% were seropositive for AAV6, and 10-20% were seropositive for AAV5. CF children were seropositive for AAV type 2, 5, or 6 at rates of 4-15%. All individuals seropositive for AAV6 were also seropositive for AAV2, and the AAV6 titer was low compared with the AAV2 titer. AAV5-positive sera were lower both in titers and rates than those seen for AAV6. The results indicate that AAV type 2, 5 or 6 exposure is low in CF and control populations and even lower in CF children.
Background
Hyperglycaemia may contribute to failure to recover from pulmonary exacerbations in cystic fibrosis (CF). We aimed to evaluate the prevalence and mechanism of hyperglycaemia during and ...post‐exacerbations.
Methods
Nine paediatric CF patients, not on insulin, hospitalized for intravenous antibiotics, underwent an oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM) upon admission (visit 1) and an OGTT 2 weeks (visit 2) and 6 weeks to 12 months later when at stable baseline (visit 3). Insulin and glucose levels were measured before, 30, 60 and 120 min after glucose ingestion during OGTT. Hyperglycaemia on OGTT was defined according to the American Diabetes Association criteria as abnormal OGTT or consistent with diabetes. Hyperglycaemia on CGM was defined as CGM time above 140 mg/dL > 4.5%.
Results
At visit 1, 8/9 patients had hyperglycaemia on both CGM and OGTT (2 diabetes and 6 abnormal OGTT). At visit 2, 5/8 had hyperglycaemia (all abnormal OGTT). At visit 3, (median (IQR) time since visit 1, 4.9 (3.8‐6.3) months), 5/7 had hyperglycaemia (2 diabetes and 3 abnormal OGTT). At visits 1, 2 and 3, respectively, mean (SD) 2‐hour OGTT glucose was 175.8 (42.3), 146.3 (31.9) and 176.9 (51.7) mg/dL. CGM time above 140 mg/dL at visit 1 was 25.3% (16.9). Insulin AUC decreased from visit 2 (median (IQR) 5449 (3321‐8123) mcIU‐min/mL) to visit 3 (3234 (2913‐3680) mcIU‐min/mL).
Conclusion
Hyperglycaemia is prevalent during paediatric CF exacerbations; it appears to improve with exacerbation treatment but to worsen later in association with decreased insulin secretion.
In this study, we evaluate the prevalence and mechanism of hyperglycaemia during and post‐cystic fibrosis exacerbations. We found that hyperglycaemia is prevalent during paediatric CF exacerbations using both oral glucose tolerance tests and continuous glucose monitoring. It appears to improve with exacerbation treatment but to worsen later in association with decreased insulin secretion.
Deep vein thrombosis (DVT) is defined as a blood clot that occurs in a deep vein in the body, often in the leg or thigh; a pulmonary embolism (PE), however, occurs when a clot breaks free and enters ...the arteries of the lungs. The prevention of DVT and PE should be a priority for the entire health care profession.
PDF
