d; and Consejo Superior de Investigaciones Científicas, Madrid, Spain e Streptococcus pneumoniae plays an important role in causing acute exacerbations in patients with chronic respiratory disease. However, few data are available regarding pneumococcal persistence in adult patients with chronic respiratory diseases. Fifty pneumococci recovered from sputum samples (1995 to 2010) from 13 adult patients with >3 episodes of acute exacerbation or pneumonia, with the same serotype and pulsed-field gel electrophoresis (PFGE) pattern, were studied. Multilocus sequence typing (MLST) loci, penicillin-binding protein (PBP) genes (pbp2x, pbp1a, pbp2b), and the quinolone-resistant determining regions (QRDRs) of parC, parE, and gyrA were PCR amplified and sequenced. The average time between the first and last episode was 582 days (standard deviation [SD], ؎362). All but two patients received multiple courses of -lactam treatment, and all persistent strains were resistant to penicillin; however, the PBP sequences were stable over time apart from one variable nucleotide in pbp2x, observed among pneumococci isolated from three patients. In contrast, 7/11 patients treated with fluoroquinolones had fluoroquinolone-resistant pneumococci. In three patients, the initially fluoroquinolone-susceptible strain developed resistance after fluoroquinolone therapy, and in the remaining four patients, the persistent strain was fluoroquinolone resistant from the first episode. QRDR changes involved in fluoroquinolone resistance were frequently observed in persistent strains after fluoroquinolone treatment; however, the PBP sequences and MLST genotypes of these strains were stable over time.
Patients with chronic respiratory disease, such as chronic obstructive pulmonary disease (COPD) and bronchiectasis, are often persistently colonized by respiratory pathogens (27, 32). Airway colonization, mainly by Pseudomonas aeruginosa, Haemophilus influenzae, and Streptococcus pneumoniae, contributes to progressive pulmonary damage, increasing the morbidity and the risk of death of these patients due to frequent and recurrent episodes of acute exacerbations (27).Most of the acute exacerbations caused by P. aeruginosa are due to a preexisting strain which colonizes the lower airway. Often, these strains are hypermutable (strains with defects in genes involved in DNA repair) and have been related to an increase of antimicrobial resistance due to a stepwise accumulation of point mutations (28). In contrast, when S. pneumoniae has been recovered during an acute exacerbation, this has generally been associated with the acquisition of a new strain, and the high prevalence of multidrug-resistant pneumococci associated with acute exacerbations has been related to the consumption of antimicrobials that these patients receive as empirical treatment (18, 26). The role of pneumococcal hypermutable strains is unclear and could be related to the persistent strains that colonize among 15 to 17% of COPD patients at any time (12,32).Antimicrobial treatment for acute exa...