Infection Control in Cystic Fibrosis: Cohorting, Cross-Contamination, and the Respiratory Therapist

Department of Respiratory Care, Children's Memorial Hospital, 2300 Children's Plaza, Box 58, Chicago, IL 60614, USA.
Respiratory care (Impact Factor: 1.84). 06/2009; 54(5):641-57. DOI: 10.4187/aarc0446
Source: PubMed


Cystic fibrosis (CF) is a complex genetic disease characterized by lung infections that lead to early morbidity and death. Pathogens that commonly infect the lungs of patients with CF include Staphylococcus aureus, Haemophilus influenzae, Pseudomonas aeruginosa, and Burkholderia cepacia. Aggressively treating pulmonary infection with antibiotics has contributed to improved survival in patients with CF but has also promoted multiple-drug-resistant bacteria. Other complexities include the ability of bacteria to form biofilms, which makes them more resistant to antibiotics, and emerging pathogens in CF, of which the clinical importance is not yet clear. Increasing evidence of patient-to-patient transmission of CF pathogens led the Cystic Fibrosis Foundation to produce evidence-based infection-control recommendations, which stress 4 principles: standard precautions, transmission-based precautions, hand hygiene, and care of respiratory equipment. Respiratory therapists need to know and follow these infection-control recommendations. Cohorting patients infected with B. cepacia complex is one of several interventions successful at keeping the spread of this pathogen low, but cohorting patients who are infected/colonized with other microbes is controversial, the main argument of which is not being certain of a patient's present respiratory culture status at any given patient visit.

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    • "It is characterized by abnormal transport of chloride and sodium across epithelium, leading to thick, viscous secretions [1]. The hallmark pulmonary symptoms of CF are accumulation of thick, sticky mucus , frequent chest infections and coughing or shortness of breath [2]. Such pulmonary infections are the primary cause of morbidity and mortality among patients with CF; endobronchial infection with Pseudomonas aeruginosa is difficult to treat since aminoglycosides active against P. aeruginosa penetrate sputum poorly. "
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    ABSTRACT: Cystic fibrosis (CF) patients are suffering from multiple often chronic endobronchial infection. The stiff mucus in these patients represents a compartment, which cannot easily be reached by systemic treatment. While bacterial infections are now successfully treated with repeated inhalation of antibiotics such as tobramycine, 57% of CF patients are colonized by Aspergillus species. About 10-20% of colonized patients develop symptoms of allergic bronchopulmonary aspergillosis (ABPA). While current standard of treatment of ABPA in CF patients is to suppress the allergy related symptoms by administration of glucocorticoids, itraconazole (ITRA), administered orally at high doses, can alleviate the symptoms of ABPA. However, no inhalable formulation of ITRA is available to enable local treatment of aspergillosis. The aim of this study was to describe an aqueous nanosuspension of ITRA and to characterize the pharmacokinetics after single dose inhalation. Using wet-milling with organic milling beads, a stable nanosuspension with particle size in the range of 200nm and an ITRA concentration of 20% (v/w) could be obtained, using polysorbate 80 at a concentration of 14% relative to ITRA. The suspension was stable if stored at 8°C for 3months without particle growth and could be nebulized using standard nebulizer technologies including mesh technology and pressured air nebulizers. A 10% suspension was well tolerated upon repeated dose inhalation once daily for 7days at a predicted dose of 45mg/kg in rats. A single dose inhalation at a predicted dose of 22.5mg/kg resulted in maximum lung tissue concentration of 21.4μg/g tissue with a terminal half-life of 25.4h. Serum concentrations were lower, with a maximum concentration of 104ng/ml at 4h after dosing and a terminal half-life of 10.5h. The data indicate that ITRA nanosuspension represents an interesting formulation for inhaled administration in CF patients suffering from ABPA. High and long lasting lung tissue concentrations well above the minimal inhibitory concentration of Aspergillus species enable once daily administration with minimal systemic exposure.
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    • "The presence of this defective channel in the body leads to diverse symptoms involving many organ systems and tissues, mainly due to the buildup of fluids throughout the body. The backup of fluid contributes to other serious ailments including increased susceptibility to infections and various breathing problems [20]. "
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    ABSTRACT: Many serious diseases have a genetic basis which, from an evolutionary point of view, should have been selected against, resulting in very low frequencies. The remarkable sustained prevalence of a number of disease-associated alleles is therefore surprising. We believe that antagonistic pleiotropy, when multiple effects of a gene have opposing effects on fitness (e.g., sickle cell disease), may be more widespread than typically considered. We hypothesize that, rather than being an exception to the rule of genetic disorders, antagonistic pleiotropy may be common. We surveyed the medical literature in order to determine whether sufficient evidence exists to reassess the nature of antagonistic pleiotropy; from being considered an unusual scenario to one that is anticipated. We also used a simple population genetic model to examine the feasibility of antagonistic pleiotropy to act as a mechanism to maintain polymorphism for serious genetic disorders even if the benefits are subtle. We identified a number of examples of antagonistic pleiotropy where the deleterious effect, the beneficial effect, and the exact molecular cause have been demonstrated. We also identified putative cases in which there is circumstantial evidence or a strong reason to expect antagonistic pleiotropy in a genetic disorder. The population genetic model demonstrates that alleles with severe deleterious health effects can be maintained at medically relevant frequencies with only minor beneficial pleiotropic effects. We believe that our identification of several cases of antagonistic pleiotropy, despite the lack of research on this question and the varied natures of the types of these disorders, speaks to both the underappreciated nature of this phenomenon and its potentially fundamental importance. If antagonistic pleiotropy is as common as our research suggests, this may explain why so many serious diseases, even apparently environmentally caused ones, have a genetic component. Furthermore, acceptance of a genome full of antagonistically pleiotropic genetic interactions poses important implications for clinical treatment and disease prevention research, especially genetically based therapies.
    BMC Medical Genetics 12/2011; 12(1):160. DOI:10.1186/1471-2350-12-160 · 2.08 Impact Factor
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    Intelligent Robots and Systems, 2001. Proceedings. 2001 IEEE/RSJ International Conference on; 02/2001
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