Dynamics of Long-Term Colonization of Respiratory Tract by Haemophilus influenzaein Cystic Fibrosis Patients Shows a Marked Increase in Hypermutable Strains

Autor: Roma´n, Federico, Canto´n, Rafael, Pe´rez-Va´zquez, Mari´a, Baquero, Fernando, Campos, Jose´
Zdroj: Journal of Clinical Microbiology; April 2004, Vol. 42 Issue: 4 p1450-1459, 10p
Abstrakt: ABSTRACTThe persistence and variability of 188 Haemophilus influenzaeisolates in respiratory tract of 30 cystic fibrosis (CF) patients over the course of 7 years was studied. Antibiotic susceptibility testing, DNA fingerprinting, and analysis of outer membrane protein profiles were performed on all isolates. A total of 115 distinct pulsed-field gel electrophoresis profiles were identified. Ninety percent of patients were cocolonized with two or more clones over the studied period. A third of the patients were cross-colonized with one or two H. influenzaestrains; 11% of the clones persisted for 3 or more months. Biotype, outer membrane protein profiles, and resistance profiles showed variation along the studied period, even in persisting clones. Four isolates (2.1%) recovered from 3 patients were type f capsulate, with three of them belonging to the same clone. ß-Lactamase production was detected in 23.9% of isolates while 7% of the ß-lactamase-negative isolates presented diminished susceptibility to ampicillin (ß-lactamase-negative ampicillin resistance phenotype). Remarkably, 21.3% of the H. influenzaeisolates presented decreased susceptibility to ciprofloxacin, which was mainly observed in persisting clones. Of the H. influenzaeisolates from CF patients, 18 (14.5%) were found to be hypermutable in comparison with 1 (1.4%) from non-CF patients (P< 0.0001). Ten patients (33.3%) were colonized by hypermutable strains over the study period. A multiresistance phenotype and long-term clonal persistence were significantly associated in some cases for up to 7 years. These results suggest that H. influenzaebronchial colonization in CF patients is a dynamic process, but better-adapted clones can persist for long periods of time.
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