Complications and Practice Variation in the Use of Peripherally Inserted Central Venous Catheters in People With Cystic Fibrosis: The Prospective Study of Peripherally Inserted Venous Catheters in People With Cystic Fibrosis Study.

BACKGROUND: Peripherally inserted central catheters (PICCs) are used commonly to administer antibiotics to people with cystic fibrosis (CF), but their use can be complicated by venous thrombosis and catheter occlusion. RESEARCH QUESTION: Which participant-, catheter-, and catheter management-level attributes are associated with increased risk of complications of PICCs among people with CF? STUDY DESIGN AND METHODS: This was a prospective observational study of adults and children with CF who received PICCs at 10 CF care centers in the United States. The primary end point was defined as occlusion of the catheter resulting in unplanned removal, symptomatic venous thrombosis in the extremity containing the catheter, or both. Three categories of composite secondary outcomes were identified: difficult line placement, local soft tissue or skin reactions, and catheter malfunction. Data specific to the participant, catheter placement, and catheter management were collected in a centralized database. Risk factors for primary and secondary outcomes were analyzed by multivariate logistic regression. RESULTS: Between June 2018 and July 2021, 157 adults and 103 children older than 6 years with CF had 375 PICCs placed. Patients underwent 4,828 catheter-days of observation. Of the 375 PICCs, 334 (89%) were ≤ 4.5 F, 342 (91%) were single lumen, and 366 (98%) were placed using ultrasound guidance. The primary outcome occurred in 15 PICCs for an event rate of 3.11 per 1,000 catheter-days. No cases of catheter-related bloodstream infection occurred. Other secondary outcomes developed in 147 of 375 catheters (39%). Despite evidence of practice variation, no risk factors for the primary outcome and few risk factors for secondary outcomes were identified. INTERPRETATION: This study affirmed the safety of contemporary approaches to inserting and using PICCs in people with CF. Given the low rate of complications in this study, observations may reflect a widespread shift to selecting smaller-diameter PICCs and using ultrasound to guide their placement.

Financial impacts of the COVID-19 pandemic on cystic fibrosis care: lessons for the future.

BACKGROUND: Chronic care delivery models faced unprecedented financial pressures, with a reduction of in-person visits and adoption of telehealth during the COVID-19 pandemic. We sought to understand the reported financial impact of pandemic-related changes to the cystic fibrosis (CF) care model. METHODS: The U.S. CF Foundation State of Care surveys fielded in Summer 2020 (SoC1) and Spring 2021 (SoC2) included questions for CF programs on the impact of pandemic-related restrictions on overall finances, staffing, licensure, and reimbursement of telehealth services. Descriptive analyses were conducted based on program type. RESULTS: Among the 286 respondents (128 pediatric, 118 adult, 40 affiliate), the majority (62%) reported a detrimental financial impact to their CF care program in SoC1, though fewer (42%) reported detrimental impacts in SoC2. The most common reported impacts in SoC1 were redeployment of clinical staff (68%), furloughs (52%), hiring freezes (51%), decreases in salaries (34%), or layoffs (10%). Reports of lower reimbursement for telehealth increased from 30% to 40% from SoC1 to SoC2. Projecting towards the future, only a minority (17%) of program directors in SoC2 felt that financial support would remain below pre-pandemic levels. CONCLUSIONS: The COVID-19 pandemic resulted in financial strain on the CF care model, including challenges with reimbursement for telehealth services and reductions in staffing due to institutional changes. Planning for the future of CF care model needs to address these short-term impacts, particularly to ensure a lack of interruption in high-quality multi-disciplinary care.

Rapid lung function decline in adults with early-stage cystic fibrosis lung disease.

RATIONALE: The prevalence of adults living with cystic fibrosis (CF) who have early-stage lung disease is increasing. OBJECTIVES: Describe the prevalence and evaluate spirometric risk factors associated with the subgroup of patients with early-stage lung disease and FEV1 decline of ≥5% predicted/year. METHODS: Retrospective cohort study of patients ≥18 years with FEV1% predicted ≥80% included in the US CF Foundation Patient Registry from 2010-2013. Regression models were developed to estimate FEV1 rate of decline. Multivariable logistic analysis was used to assess if spirometric risk factors were associated with FEV1 decline. MEASUREMENTS AND MAIN RESULTS: 3,029 subjects were in the study cohort. Approximately 15% of the cohort had a substantial decline in lung function ≥5% predicted/year. In multivariable models adjusted for confounders, FEV1/FVC ratio <0.8 (Odds Ratio (OR) 1.63, 95% confidence interval (CI) 1.31 to 2.02) and history of FEV1% predicted variability (OR 2.35,95%CI 1.74 to 3.18) were associated with rapid lung function decline. CONCLUSIONS: Even among adults with early-stage lung disease, approximately 15% are shown to progress and experience a large decline in lung function. This reinforces the concept that lung function in early-stage CF is not normal or mild. Rather, lung function decline may be delayed, but not avoided, in these individuals. Variability in FEV1% predicted and airway obstruction as measured by FEV1/FVC ratio may identify individuals at increased risk of decline. Adults with early-stage lung disease should be followed in clinic to monitor for onset of decline.

Eradication of persistent methicillin-resistant Staphylococcus aureus infection in cystic fibrosis.

BACKGROUND: The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in individuals with cystic fibrosis (CF) has increased significantly. While studies demonstrate that persistent MRSA infection in CF is associated with poor clinical outcomes, there are no randomized controlled studies informing management. METHODS: The Persistent MRSA Eradication Protocol was a double-blind, randomized, placebo-controlled study investigating a comprehensive 28-day treatment regimen with or without inhaled vancomycin for eradication of MRSA. Eligible participants had CF and documented persistent MRSA infection. All participants received oral antibiotics, topical decontamination, and environmental cleaning and were randomized to receive inhaled vancomycin or inhaled placebo. The primary outcome was the difference in MRSA eradication rates one month after completion of the treatment protocol. RESULTS: 29 participants were randomized. Four subjects in the inhaled vancomycin group required withdrawal from the study for bronchospasm before outcome data were collected and were excluded from analysis. There was no difference in the primary outcome: 2/10 (20%) of subjects in the intervention group and 3/15 (20%) in the placebo group had a MRSA negative sputum culture one month after treatment. There were no statistically significant differences in the rates of MRSA eradication at the end of treatment or three months after treatment completion. CONCLUSIONS: This study suggests that persistent MRSA infection is difficult to eradicate, even with multimodal antibiotics. The use of a single course of inhaled vancomycin may not lead to higher rates of MRSA eradication in individuals with CF and may be associated with bronchospasm. FUND: This trial was financially supported by the Cystic Fibrosis Foundation.

Cystic fibrosis patient registries: A valuable source for clinical research.

Cystic Fibrosis (CF) patient registries are valuable data sources for researchers studying the natural history, treatment paradigms, and long-term health outcomes of individuals with CF. In this review, we discuss the role of CF patient registries in facilitating comparative effectiveness research, particularly evaluating therapies and variation in health care delivery. We also discuss the limitations of registry-based research, particularly indication bias, as well as statistical methods that can be used to address these issues.

Standardized Treatment of Pulmonary Exacerbations (STOP) study: Physician treatment practices and outcomes for individuals with cystic fibrosis with pulmonary Exacerbations.

BACKGROUND: Pulmonary Exacerbations (PEx) are associated with increased morbidity and mortality in individuals with CF. PEx management practices vary widely, and optimization through interventional trials could potentially improve outcomes. The object of this analysis was to evaluate current physician treatment practices and patient outcomes for PEx. METHODS: The Standardized Treatment of Pulmonary Exacerbations (STOP) observational study enrolled 220 participants ≥12years old admitted to the hospital for PEx at 11 U.S. CF centers. Spirometry and daily symptom scores were collected during the study. Physicians were surveyed on treatment goals and their management practices were observed. Treatment outcomes were compared to stated goals. RESULTS: The mean (SD) duration of IV antibiotic treatment was 15.9 (6.0) days. Those individuals with more severe lung disease (<50% FEV1) were treated nearly two days longer than those with >50% FEV1. Physician-reported FEV1 improvement goals were 10% (95% CI: 5%, 14%) lower for patients with 6-month baseline FEV1 ≤50% predicted compared with those with 6-month baseline FEV1 >50% predicted. There were clinically and statistically significant improvements in symptoms from the start of IV antibiotic treatment to the end of IV antibiotic treatment and 28days after the start of treatment. The mean absolute increase in FEV1 from admission was 9% predicted at end of IV antibiotic treatment, and 7% predicted at day 28. Only 39% fully recovered lost lung function, and only 65% recovered at least 90% of lost lung function. Treatment was deemed successful by 84% of clinicians, although 6-month baseline FEV1 was only recovered in 39% of PEx. CONCLUSIONS: In this prospective observational study of PEx, treatment regimens and durations showed substantial variation. A significant proportion of patients did not reach physician's treatment goals, yet treatment was deemed successful.

Preliminary comparison of normalized T1 and non-contrast perfusion MRI assessments of regional lung disease in cystic fibrosis patients.

BACKGROUND: Previous studies have shown that Magnetic Resonance Imaging (MRI) techniques can be used to non-invasively assess lung disease in CF patients. In this study, we compare the sensitivity of normalized T1 (nT1) and non-contrast perfusion MRI techniques to detect regional lung disease in CF patients. MATERIALS AND METHODS: MRI data were obtained for eight adult CF patients without overt pulmonary exacerbation (FEV1=45-127%) and six healthy volunteers on a Siemens Espree 1.5T MRI scanner. Sagittal nT1 and perfusion data were acquired for each subject's left and right lungs. A region-of-interest analysis was used to calculate mean nT1 and perfusion values in the individual lobes of the left and right lungs for each subject. RESULTS: In comparison to healthy controls, CF subjects showed a significant decrease in nT1 values in the upper lobe of the left lung as well as in the upper and anterior lobes of the right lung (p<0.001). Similar nT1 differences were observed with in the CF cohort in comparison to their respective posterior lobes (p<0.001). Pulmonary perfusion for the CF subjects was also significantly reduced in the upper lobe of the right lung (p<0.05). Significant correlations with spirometry were also observed for both nT1 (left upper lobe: p<0.01) and perfusion (left and right upper lobes (p≤0.05)). Additionally, significant correlations were observed between nT1 and perfusion in the upper lobes of the left (p=0.05) and right lungs (p=0.005). CONCLUSIONS: This pilot study confirms that both the nT1 and non-contrast perfusion MRI techniques can sensitively detect regional lung changes in patients with CF. While both imaging methods were able to detect regional lung disease, the additional nT1 reductions in the CF patients suggests that nT1 may be more sensitive to regional CF lung disease.

Impact of lung allocation score on survival in cystic fibrosis lung transplant recipients.

BACKGROUND: The lung allocation score (LAS) has changed organ allocation for lung transplantation in the United States. Previous investigations of transplant recipients reported an association between high LAS and an increased risk of death after lung transplantation. We hypothesize that a high LAS predicts survival in lung transplant recipients with cystic fibrosis (CF) in the United Network for Organ Sharing Scientific Registry of Transplant Recipients database. METHODS: A cohort study was conducted of 1,437 U.S. adult lung transplant recipients with CF from May 1, 2005, through December 31, 2012. The cohort was divided into a high-risk group and a low-risk group based on LAS. Survival data were examined using Kaplan-Meier estimates and Cox proportional hazard models to compare survival. The primary outcome was adjusted survival at 1 year after lung transplantation. RESULTS: The high-risk group of 318 patients with a median LAS of 69.6 (interquartile range 56.3-87.2) was compared with a low-risk group of 1,119 patients with a median LAS of 38.8 (interquartile range 36.3-42.3). Patients in the high-risk group had a 41% increased relative risk of cumulative mortality at 1 year after transplantation compared with the low-risk group (16.1% vs 12.0%). After adjustment for known predictors of mortality, the risk of death at 1 year after transplantation remained elevated (hazard ratio = 1.41; 95% confidence interval = 1.00-2.01). The high-risk group had worse survival at 90 days and 2 years after lung transplantation. CONCLUSIONS: High LAS are associated with worse survival in lung transplant recipients with CF.

Association between the introduction of a new cystic fibrosis inhaled antibiotic class and change in prevalence of patients receiving multiple inhaled antibiotic classes.

BACKGROUND: In 2010, aztreonam for inhalation solution joined aminoglycosides and colistimethate as a new cystic fibrosis (CF) chronic inhaled antimicrobial therapy. We studied how the introduction of this new inhaled antibiotic class changed the management of US CF patients. METHODS: The use of inhaled aminoglycosides, colistimethate, and aztreonam among patients followed in the CF Foundation Patient Registry was analyzed by age group, lung disease stage, and microbiologic status both annually, and at individual visits between 2009 and 2012. RESULTS: The overall prevalence of inhaled antibiotic use did not change during the period, but the prevalence of annual and any visit treatment with >1 inhaled antibiotic class more than doubled. Adults, those with advanced lung disease, and those with >1 Pseudomonas aeruginosa respiratory culture were more likely to receive >1 antibiotic class. CONCLUSIONS: Inhaled antibiotic management of US CF patients has dramatically changed in association with the introduction of a third inhaled antibiotic class.

Antibiotic management of lung infections in cystic fibrosis. I. The microbiome, methicillin-resistant Staphylococcus aureus, gram-negative bacteria, and multiple infections.

Despite significant advances in treatment strategies targeting the underlying defect in cystic fibrosis (CF), airway infection remains an important cause of lung disease. In this two-part series, we review recent evidence related to the complexity of CF airway infection, explore data suggesting the relevance of individual microbial species, and discuss current and future treatment options. In Part I, the evidence with respect to the spectrum of bacteria present in the CF airway, known as the lung microbiome is discussed. Subsequently, the current approach to treat methicillin-resistant Staphylococcus aureus, gram-negative bacteria, as well as multiple coinfections is reviewed. Newer molecular techniques have demonstrated that the airway microbiome consists of a large number of microbes, and the balance between microbes, rather than the mere presence of a single species, may be relevant for disease pathophysiology. A better understanding of this complex environment could help define optimal treatment regimens that target pathogens without affecting others. Although relevance of these organisms is unclear, the pathologic consequences of methicillin-resistant S. aureus infection in patients with CF have been recently determined. New strategies for eradication and treatment of both acute and chronic infections are discussed. Pseudomonas aeruginosa plays a prominent role in CF lung disease, but many other nonfermenting gram-negative bacteria are also found in the CF airway. Many new inhaled antibiotics specifically targeting P. aeruginosa have become available with the hope that they will improve the quality of life for patients. Part I concludes with a discussion of how best to treat patients with multiple coinfections.

Antibiotic management of lung infections in cystic fibrosis. II. Nontuberculous mycobacteria, anaerobic bacteria, and fungi.

Airway infections are a key component of cystic fibrosis (CF) lung disease. Whereas the approach to common pathogens such as Pseudomonas aeruginosa is guided by a significant body of evidence, other infections often pose a considerable challenge to treating physicians. In Part I of this series on the antibiotic management of difficult lung infections, we discussed bacterial organisms including methicillin-resistant Staphylococcus aureus, gram-negative bacterial infections, and treatment of multiple bacterial pathogens. Here, we summarize the approach to infections with nontuberculous mycobacteria, anaerobic bacteria, and fungi. Nontuberculous mycobacteria can significantly impact the course of lung disease in patients with CF, but differentiation between colonization and infection is difficult clinically as coinfection with other micro-organisms is common. Treatment consists of different classes of antibiotics, varies in intensity, and is best guided by a team of specialized clinicians and microbiologists. The ability of anaerobic bacteria to contribute to CF lung disease is less clear, even though clinical relevance has been reported in individual patients. Anaerobes detected in CF sputum are often resistant to multiple drugs, and treatment has not yet been shown to positively affect patient outcome. Fungi have gained significant interest as potential CF pathogens. Although the role of Candida is largely unclear, there is mounting evidence that Scedosporium species and Aspergillus fumigatus, beyond the classical presentation of allergic bronchopulmonary aspergillosis, can be relevant in patients with CF and treatment should be considered. At present, however there remains limited information on how best to select patients who could benefit from antifungal therapy.

Eradication strategy for persistent methicillin-resistant Staphylococcus aureus infection in individuals with cystic fibrosis--the PMEP trial: study protocol for a randomized controlled trial.

BACKGROUND: The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) respiratory infection in cystic fibrosis (CF) has increased dramatically over the last decade, and is now affecting approximately 25% of patients. Epidemiologic evidence suggests that persistent infection with MRSA results in an increased rate of decline in FEV1 and shortened survival. Currently, there are no conclusive studies demonstrating an effective and safe treatment protocol for persistent MRSA respiratory infection in CF. METHODS/DESIGN: The primary objective of this study is to evaluate the safety and efficacy of a 28-day course of vancomycin for inhalation in combination with oral antibiotics in eliminating MRSA from the respiratory tract of individuals with CF and persistent MRSA infection. This is a two-center, randomized, double-blind, comparator-controlled, parallel-group study with 1:1 assignment to either vancomycin for inhalation (250 mg twice a day) or taste-matched placebo for 28 days in individuals with cystic fibrosis. In addition, both groups will receive oral rifampin, a second oral antibiotic - trimethoprim/sulfamethoxazole (TMP/SMX) or doxycycline, protocol determined - mupirocin intranasal cream, and chlorhexidine body washes. Forty patients with persistent respiratory tract MRSA infection will be enrolled: 20 will be randomized to vancomycin for inhalation and 20 to a taste-matched placebo. The primary outcome will be the presence of MRSA in sputum respiratory tract cultures 1 month after the conclusion of treatment. Secondary outcomes include the efficacy of the intervention on: FEV1% predicted, patient reported outcomes, pulmonary exacerbations, and MRSA colony-forming units found in respiratory tract sample culture. DISCUSSION: Results of this study will provide guidance to clinicians regarding the safety and effectiveness of a targeted eradication strategy for persistent MRSA infection in CF. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (NCT01594827, received 05/07/2012) and is funded by the Cystic Fibrosis Foundation (Grants: PMEP10K1 and PMEP11K1).

Normalized T1 magnetic resonance imaging for assessment of regional lung function in adult cystic fibrosis patients--a cross-sectional study.

BACKGROUND: Cystic fibrosis (CF) patients would benefit from a safe and effective tool to detect early-stage, regional lung disease to allow for early intervention. Magnetic Resonance Imaging (MRI) is a safe, non-invasive procedure capable of providing quantitative assessments of disease without ionizing radiation. We developed a rapid normalized T1 MRI technique to detect regional lung disease in early-stage CF patients. MATERIALS AND METHODS: Conventional multislice, pulmonary T1 relaxation time maps were obtained for 10 adult CF patients with normal spirometry and 5 healthy non-CF control subjects using a rapid Look-Locker MRI acquisition (5 seconds/imaging slice). Each lung absolute T1 map was separated into six regions of interest (ROI) by manually selecting upper, central, and lower lung regions in the left and right lungs. In order to reduce the effects of subject-to-subject variation, normalized T1 maps were calculated by dividing each pixel in the absolute T1 maps by the mean T1 time in the central lung region. The primary outcome was the differences in mean normalized T1 values in the upper lung regions between CF patients with normal spirometry and healthy volunteers. RESULTS: Normalized T1 (nT1) maps showed visibly reduced subject-to-subject variation in comparison to conventional absolute T1 maps for healthy volunteers. An ROI analysis showed that the variation in the nT1 values in all regions was ≤2% of the mean. The primary outcome, the mean (SD) of the normalized T1 values in the upper right lung regions, was significantly lower in the CF subjects [.914 (.037)] compared to the upper right lung regions of the healthy subjects [.983 (.003)] [difference of .069 (95% confidence interval .032-.105); p = .001). Similar results were seen in the upper left lung region. CONCLUSION: Rapid normalized T1 MRI relaxometry obtained in 5 seconds/imaging slice may be used to detect regional early-stage lung disease in CF patients.

Isoflurane and ketamine anesthesia have different effects on ventilatory pattern variability in rats.

We hypothesize that isoflurane and ketamine impact ventilatory pattern variability (VPV) differently. Adult Sprague-Dawley rats were recorded in a whole-body plethysmograph before, during and after deep anesthesia. VPV was quantified from 60-s epochs using a complementary set of analytic techniques that included constructing surrogate data sets that preserved the linear structure but disrupted nonlinear deterministic properties of the original data. Even though isoflurane decreased and ketamine increased respiratory rate, VPV as quantified by the coefficient of variation decreased for both anesthetics. Further, mutual information increased and sample entropy decreased and the nonlinear complexity index (NLCI) increased during anesthesia despite qualitative differences in the shape and period of the waveform. Surprisingly mutual information and sample entropy did not change in the surrogate sets constructed from isoflurane data, but in those constructed from ketamine data, mutual information increased and sample entropy decreased significantly in the surrogate segments constructed from anesthetized relative to unanesthetized epochs. These data suggest that separate mechanisms modulate linear and nonlinear variability of breathing.

Update on methicillin-resistant Staphylococcus aureus in cystic fibrosis.

PURPOSE OF REVIEW: Respiratory infection is a major contributor to morbidity and mortality in cystic fibrosis (CF). One infection the CF community is particularly concerned about is methicillin-resistant Staphylococcus aureus (MRSA). Worldwide, the prevalence of MRSA has been rising and the impact on clinical outcomes and optimal prevention and treatment strategies are unclear. RECENT FINDINGS: Studies have demonstrated MRSA is independently associated with poor clinical outcomes, even after taking into account severity of illness. Additionally, characteristics of MRSA strains, such as small colony variants and borderline oxacillin-resistant S. aureus, may be important in predicting the subsequent clinical course. The treatment of MRSA has had variable results and emergence of resistance to commonly prescribed antibiotics is a concern. SUMMARY: The evidence to date supports MRSA infection is independently associated with worse outcomes. The next step is to build upon the current research to expand the knowledge about the impact different strains of MRSA have on infection control strategies and MRSA treatment protocols. Interventions should balance patient safety, efficacy, and treatment burden to improve the quality and length of life in patients with CF.

Higher PEEP in patients with acute lung injury: a systematic review and meta-analysis.

BACKGROUND: Studies of ventilation strategies that included higher PEEP in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) have yielded conflicting results. OBJECTIVE: To determine whether higher PEEP during volume-limited and pressure-limited ventilation is associated with 28-day mortality or barotrauma rates in patients with ALI/ARDS. METHODS: We searched MEDLINE, CENTRAL, EMBASE, CINAHL, Web of Science, and the bibliographies of retrieved papers to identify randomized controlled trials that compared higher and lower PEEP in adult patients with ALI/ARDS who were already receiving volume-limited or pressure-limited ventilation. Two of us independently abstracted study-level data, including study design, patient characteristics, study methods, intervention, and main results. We pooled the study-level data with a random-effects model, unless heterogeneity was low (I(2) < 50%), in which case we used a fixed-effects model. The primary outcome was 28-day mortality. RESULTS: Four randomized trials (2,360 participants) were evaluated. Higher PEEP had a nonsignificant trend toward lower 28-day mortality (pooled relative risk 0.90, 95% CI 0.79-1.02). There was no difference in barotrauma between the 2 groups (pooled relative risk 1.17, 95% CI 0.90-1.52). Two studies reported an adjusted hospital death rate, and the pooled results of sensitivity analysis with those adjusted rates were identical to those of the unadjusted analysis. CONCLUSIONS: In 4 recent studies that used volume-limited or pressure-limited ventilation in ALI/ARDS patients, higher PEEP was not associated with significantly different short-term mortality or barotrauma. This study does not support the routine use of higher PEEP in patients with ALI/ARDS.

Association between respiratory tract methicillin-resistant Staphylococcus aureus and survival in cystic fibrosis.

CONTEXT: The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the respiratory tract of individuals with cystic fibrosis (CF) has increased dramatically; however, its impact on outcomes in CF is unclear. Because the time between infection with bacteria in CF and death can be decades, observational studies with long periods of follow-up are well suited to address the current gap in knowledge. OBJECTIVE: To determine whether isolation of MRSA from the respiratory tract of CF patients is associated with worse survival compared with patients who never have a culture positive for MRSA. DESIGN, SETTING, AND PARTICIPANTS: Cohort study of 19,833 CF patients aged 6 to 45 years seen at centers accredited by the Cystic Fibrosis Foundation in the United States. Patients entered between January 1996 and December 2006 and were followed up through December 2008. Cox regression models with time-varying covariates were used to compare survival between CF patients with and without respiratory tract MRSA. MAIN OUTCOME MEASURE: Time from age at entry until age at death from any cause. RESULTS: In 137,819 patient-years of observation (median, 7.3 years/patient), 2537 CF patients died and 5759 patients had MRSA detected. The mortality rate was 18.3 deaths (95% confidence interval [CI], 17.5-19.1) per 1000 patient-years in patients without MRSA and 27.7 deaths (95% CI, 25.3-30.4) per 1000 patient-years in those with MRSA. Among those with MRSA, the attributable risk percentage of death associated with MRSA was 34.0% (95% CI, 26.7%-40.4%). The unadjusted hazard ratio associated with MRSA was 1.47 (95% CI, 1.32-1.62). After adjustment for time-varying covariates associated with severity of illness, MRSA remained associated with a higher risk of death (1.27; 95% CI, 1.11-1.45). CONCLUSION: Detection of MRSA in the respiratory tract of CF patients was associated with worse survival.

Prevalence and risk factors for recovery of filamentous fungi in individuals with cystic fibrosis.

BACKGROUND: Filamentous fungi are frequently recovered from respiratory cultures of individuals with CF. METHODS: A CF cohort database was utilized to determine filamentous fungal prevalence and risk factors. RESULTS: The prevalence of filamentous fungal isolation increased from 2.0% in 1997 to 28.7% in 2007. The odds of isolating filamentous fungi during a quarter was greater in CF adults [p<0.001], during chronic oral antibiotic use [p=0.002] and increased with each 10% drop in FEV(1) percent predicted [p=0.005], while inhaled corticosteroids surprisingly decreased the likelihood [p=0.012]. The direction of these effects persisted after excluding individuals with ABPA. A sub-analysis determined older age [p=0.019] and use of inhaled antibiotics [p=0.011] were independent risk factors for onset of fungal colonization. CONCLUSIONS: This study suggests that isolation of filamentous fungi in CF at JHH has increased and risk factors include older age, decreased lung function, and chronic oral antibiotics.