Inhaled therapies, azithromycin and Mycobacterium abscessus in cystic fibrosis patients.

Cystic fibrosis (CF) patients are at particularly high risk of developing lung disease caused by Mycobacterium abscessus complex (MABSC). Over the last 10 years, changes in CF treatment, with increasing use of inhaled therapies and low-dose azithromycin, have been accompanied by an increase in the prevalence of MABSC infections in CF patients. There is therefore some concern about the role of new CF treatments in the emergence of MABSC infections. We addressed this issue by means of a case-control study including 30 MABSC-positive cases and 60 nontuberculous mycobacteria-negative CF controls matched for age, sex and centre. We also compared practices at the CF centres with the highest prevalence of MABSC with those at the other centres. No positive association was found between MABSC lung disease and the use of inhaled therapies or low-dose azithromycin in the 4 years preceding MABSC isolation. These treatments were not significantly more frequently used at the CF centres with the highest MABSC prevalence rates. In conclusion, there is no evidence for a link between M. abscessus complex lung disease and inhaled therapies or low-dose azithromycin in patients with CF.

Mycobacterium avium and Mycobacterium abscessus complex target distinct cystic fibrosis patient subpopulations.

BACKGROUND: Clinical observations suggest that Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABSC) may affect cystic fibrosis (CF) patients with different characteristics and risk factors, but this has never been demonstrated within a single prospective cohort. METHODS: We studied 50 MABSC-positive and 23 MAC-positive patients from a French prevalence study of non-tuberculous mycobacteria (NTM) in CF. Risk factors specifically associated with MABSC and MAC were analyzed by nested case-control studies, with two NTM-negative controls matched by age, sex and center for each case. RESULTS: MAC-positive patients were significantly older than MABSC-positive patients (mean [SD] age, 23.1 [10.2] vs 17.4 [8.3] years, p=0.013), and were also older at CF diagnosis (mean [SD] age, 12.9 [16.1] vs 3.1 [7.7] years, p=0.015); they tended to be less frequent of the ΔF508/ΔF508 genotype (33.3 vs 61.1%, p=0.17) and to use pancreatic extracts less frequently (82.4 vs 97.6%, p=0.07). Risk factors identified by multivariate analysis were: i) in the MAC case-control study, an older age at CF diagnosis (p=0.004); ii) in the MABSC case-control study, at least one course of intravenous antibiotics (p=0.01) and more frequent isolation of Aspergillus (p=0.03). CONCLUSIONS: MAC affects adult patients with a mild form of CF, whereas MABSC affects younger patients with more severe CF and more frequent intravenous antimicrobial treatment.

Multicenter study of prevalence of nontuberculous mycobacteria in patients with cystic fibrosis in france.

We performed a multicenter prevalence study of nontuberculous mycobacteria (NTM) involving 1,582 patients (mean age, 18.9 years; male/female ratio, 1.06) with cystic fibrosis in France. The overall NTM prevalence (percentage of patients with at least one positive culture) was 6.6% (104/1,582 patients), with prevalences ranging from 3.7% (in the east of France) to 9.6% (in the greater Paris area). Mycobacterium abscessus complex (MABSC; 50 patients) and Mycobacterium avium complex (MAC; 23 patients) species were the most common NTM, and the only ones associated with fulfillment of the American Thoracic Society bacteriological criteria for NTM lung disease. The "new" species, Mycobacterium bolletii and Mycobacterium massiliense, accounted for 40% of MABSC isolates. MABSC species were isolated at all ages, with a prevalence peak between 11 and 15 years of age (5.8%), while MAC species reached their highest prevalence value among patients over 25 years of age (2.2%).

Continuous versus intermittent infusions of ceftazidime for treating exacerbation of cystic fibrosis.

The present multicenter, randomized crossover study compared the safety and efficacy of continuous infusion with those of short infusions of ceftazidime in patients with cystic fibrosis. Patients with chronic Pseudomonas aeruginosa colonization received two successive courses of intravenous tobramycin and ceftazidime (200 mg/kg of body weight/day) for pulmonary exacerbation administered as thrice-daily short infusions or as a continuous infusion. The primary endpoint was the variation in the forced expiratory volume in 1 s (FEV1) during the course of antibiotic treatment. Sixty-nine of the 70 patients enrolled in the study received at least one course of antibiotic treatment. The improvement in FEV1 at the end of therapy was not statistically different between the two treatment procedures (+7.6% after continuous infusion and +5.5% after short infusions) but was better after continuous ceftazidime treatment in patients harboring resistant isolates (P < 0.05). The interval between the course of antibiotic treatments was longer after the continuous infusion than after the short infusion of ceftazidime (P = 0.04). The mean serum ceftazidime concentration during the continuous infusion was 56.2 +/- 23.2 microg/ml; the mean peak and trough concentrations during the short infusions were 216.3 +/- 71.5 and 12.1 +/- 8.7 microg/ml, respectively. The susceptibility profiles of the P. aeruginosa isolates remained unchanged and were similar for both regimens. Quality-of-life scores were similar whatever the treatment procedure, but 82% of the patients preferred the continuous-infusion regimen. Adverse events were not significantly different between the two regimens. In conclusion, the continuous infusion of ceftazidime did not increase its toxicity and appeared to be as efficient as short infusions in patients with cystic fibrosis as a whole, but it gave better results in patients harboring resistant isolates of P. aeruginosa.

Long-term noninvasive ventilation in patients with cystic fibrosis.

BACKGROUND: The benefits of long-termnoninvasive positive pressure ventilation (NPPV) have not yet been evaluated in patients with cystic fibrosis (CF). OBJECTIVES: To evaluate the effect of 1 year of NPPV on lung function in patients with advanced CF. METHODS: Data were obtained from the French CF Registry. Patients who started NPPV (ventilated group, n = 41) were compared to matched controls (control group, n = 41). Each ventilated patient was matched to a control 1 year before the start of NPPV (year -1) for gender, CFTR genotype, age +/- 5 years and forced expiratory volume in 1 s (FEV(1)) +/- 10%. The ventilated group was compared to the control group at year -1, during the year of NPPV initiation (year 0) and 1 year after NPPV (year +1). RESULTS: At year -1, the two groups were comparable with regard to forced vital capacity (FVC; 43.7 vs. 49.1% in the ventilated group and the control group, respectively) and FEV(1) (28.2 vs. 28.5%). At year 0, the ventilated group had significantly greater declines in FVC (-3.6 +/- 9.2 vs. +0.8 +/- 8.9%, p = 0.03) and in FEV(1) (-3.0 +/- 6.7 vs. +2.6 +/- 4.4, p < 0.0001). At year +1, the decreases in FVC (-2.1 +/- 10.0 vs. -2.2 +/- 9.9%) and in FEV(1) (-2.2 +/- 6.7 vs. -2.3 +/- 6.2%) were similar in both groups. CONCLUSIONS: These data show that NPPV is associated with stabilization of the decrease in lung function in patients with advanced CF.

Cystic fibrosis mortality trends in France.

BACKGROUND: In 1992 France set up a national cystic fibrosis observatory (Observatoire national de la mucoviscidose, ONM) to monitor the state of health of patients on an annual basis. Using the ONM data, this study estimates the main indicators for life expectancy and assesses the total number of cystic fibrosis patients. METHODS: The data for the years 1994 to 2003 are divided into 3-year periods. Life tables are drawn up for these periods, from which mean and median lengths of life are determined. Using the most recent life table, the number of births in 2003 and the incidence of the disease, the total population of patients can be estimated, assuming a stationary population. RESULTS: In 2001-2003, life expectancy at birth of patients registered with the ONM was 39.1 years and median length of life was 36.4 years. These results, substantially better than those of 1994-1996, are linked to improved conditions of patient inclusion in the ONM database, to improvements in their healthcare, but also to the limitations of the life tables. Based on the 2003 data, the total theoretical number of patients is 6490, and coverage by the ONM database is thus 63.2%. CONCLUSIONS: These provisional results demonstrate the need to convert the ONM observatory into a registry providing exhaustive coverage of all patients.