Mortality in Adults with Cystic Fibrosis Requiring Mechanical Ventilation. Cross-Sectional Analysis of Nationwide Events.

Rationale: Survival in patients with cystic fibrosis (CF) is improving over time. Traditionally, there has been concern about high mortality in individuals with CF requiring invasive mechanical ventilation (IMV) for respiratory failure.Objectives: We hypothesized that mortality has decreased over time in this population because of improvements in disease-specific therapies.Methods: The U.S. Nationwide Healthcare Cost and Utilization Project database was used to identify adult patients with CF undergoing IMV between 2002 and 2014. Patients with nonurgent/nonemergent admissions, pregnancy, and encounters related to lung transplantation were excluded. Demographic, geographic, and comorbidities were analyzed. The Cochran-Armitage trend test was used to examine trends in mortality over time. Multivariate mixed effects logistic regression was used to account for possible differences in hospital mortality patterns.Results: We identified 58,799 CF admissions from 2002 to 2014, with 3,727 (6.3%) undergoing IMV. After exclusions, 1,711 admissions remained. In 762 (44.5%) of adult hospitalizations, the patient died. Annual mortality per hospitalization ranged from 29.9 to 55.3%. The Cochran-Armitage trend test suggested an increased probability of survival over time. Factors significantly associated with mortality in multivariate analysis included female sex (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.14-2.09), acute renal failure (OR, 1.99; 95% CI, 1.32-3.01), and malnutrition (OR, 1.44; 95% CI, 1.01-2.06). IMV greater than 96 hours was associated with increased mortality in univariate analysis (OR, 1.51; 95% CI, 1.14-1.98); however, after adjustment for potential confounders, the association was no longer statistically significant (OR, 1.05; 95% CI, 0.77-1.43).Conclusions: Mortality per hospitalization in adults with CF who are not bridging to lung transplant and require emergent IMV is 44.5%, suggesting IMV is not futile. Furthermore, mortality decreased over the study period. These finding may help providers, families, and patients with CF weigh the risks and benefits of IMV for respiratory failure.

Risk factors for persistent methicillin-resistant Staphylococcus aureus infection in cystic fibrosis.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as an important pathogen in cystic fibrosis (CF). Over 25% of individuals in the United States with CF are found to have MRSA in respiratory culture specimens, and persistent MRSA infection has been associated with more rapid decline in lung function and increased mortality. The objective of this study was to investigate clinical and demographic characteristics that are associated with the development of persistent MRSA infection in a CF population. METHODS: This was a retrospective cohort study of individuals followed from 2002 to 2012 in the Cystic Fibrosis Foundation Patient Registry. A time-to-event analysis for the development of persistent MRSA infection was performed, and multivariable Cox proportional hazards models were constructed to identify risk factors for infection. RESULTS: The study cohort included 19,434 individuals, of which 5844 would develop persistent MRSA infection. In the adjusted model, pancreatic insufficiency (HR: 1.49; 95% CI: 1.29-1.72), CF related diabetes (HR: 1.13; 95% CI: 1.05-1.20), co-infection with P. aeruginosa (HR: 1.21; 95% CI: 1.13-1.28), and number of hospitalizations/year (HR: 1.09; 95% CI: 1.06-1.12) were all associated with increased risk, whereas higher socio-economic status (HR: 0.87; 95% CI: 0.82-0.93) was associated with a lower risk. Receiving care at a CF center with increased MRSA prevalence was associated with increased risk of MRSA infection: highest quartile (HR: 2.33; 95% CI: 2.13-2.56). CONCLUSIONS: No easily modifiable risk factors for persistent MRSA were identified in this study. However, several risk factors for patients at higher risk for persistent MRSA infection were identified, for example centers with a high baseline MRSA prevalence, and may be useful in designing center-specific MRSA infection prevention and control strategies and/or eradication protocols. Additional studies are needed in order to evaluate if attention to these risk factors can improve clinical outcomes.

Emergence of linezolid-resistant Staphylococcus aureus after prolonged treatment of cystic fibrosis patients in Cleveland, Ohio.

Linezolid (LZD)-resistant Staphylococcus aureus (LRSA) isolates were monitored from 2000 to 2009 in Cleveland, OH. LRSA first emerged in 2004 only in cystic fibrosis (CF) patients, with 11 LRSA-infected CF patients being identified by 2009. LRSA was isolated from 8 of 77 CF patients with S. aureus respiratory tract infection treated with LZD from 2000 to 2006. Analysis of clinical data showed that the 8 CF patients with LRSA received more LZD courses (18.8 versus 5.9; P = 0.001) for a longer duration (546.5 versus 211.9 days; P < 0.001) and had extended periods of exposure to LZD (83.1 versus 30.1 days/year; P < 0.001) than the 69 with LZD-susceptible isolates. Five LRSA isolates included in the clinical analysis (2000 to 2006) and three collected in 2009 were available for molecular studies. Genotyping by repetitive extrapalindromic PCR and pulsed-field gel electrophoresis revealed that seven of these eight LRSA strains from unique patients were genetically similar. By multilocus sequence typing, all LRSA isolates were included in clonal complex 5 (seven of sequence type 5 [ST5] and one of ST1788, a new single-locus variant of ST5). However, seven different variants were identified by spa typing. According to the Escherichia coli numbering system, seven LRSA isolates contained a G2576T mutation (G2603T, S. aureus numbering) in one to four of the five copies of domain V of the 23S rRNA genes. One strain also contained a mutation (C2461T, E. coli numbering) not previously reported. Two strains, including one without domain V mutations, possessed single amino acid substitutions (Gly152Asp or Gly139Arg) in the ribosomal protein L3 of the peptidyltransferase center, substitutions not previously reported in clinical isolates. Emergence of LRSA is a serious concern for CF patients who undergo prolonged courses of LZD therapy.