Pseudomonas aeruginosa is the most relevant pathogen producing chronic lung infections in patients with chronic underlying diseases such as cystic fibrosis (CF), bronchiectasis, and chronic obstructive pulmonary disease (COPD). Hypermutable (or mutator) P. aeruginosa strains, characterized by increased (up to 1,000-fold) spontaneous mutation rates due to alterations of the DNA mismatch repair (MMR) system have been found at high frequencies in the lungs of CF patients, but their role in other chronic processes is still unknown. Sixty-two P. aeruginosa isolates from 30 patients with underlying non-CF chronic respiratory diseases (22 with bronchiectasis and 8 with COPD) and documented chronic infection were studied. Antibiotic susceptibility profiles and mutation frequencies were determined, and complementation assays using the cloned wild-type mutS gene and molecular epidemiology studies (pulsed-field electrophoresis, [PFGE]) were performed with these strains. Thirty-three (53%) of the isolates were hypermutable, and 17 (57%) of the 30 patients were colonized by hypermutable strains. Strains from 11 of the 17 patients were found to be defective in the MMR mutS gene by complementation assays. Interpatient transmission of strains was ruled out by PFGE. Multipleantimicrobial resistance was documented in 42% of the hypermutable strains in contrast to 0% resistance in the nonhypermutable strains (P < 0.0001). Hypermutable P. aeruginosa strains are extremely prevalent in chronic infections in contrast to what has been described in acute processes, suggesting a role of hypermutation in bacterial adaptation for long-term persistence. Furthermore, hypermutation is found to be a key factor for the development of multiple-antimicrobial resistance, and therefore these findings are expected to have important consequences for the treatment of chronic infections.

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This study examined the roles of two different diagnostic approaches to children with fever of unknown origin in determining the patterns of pneumococcal bacteraemia in two Spanish regions by comparing their main epidemiologic characteristics. Whereas a blood culture is routinely obtained in this setting in Navarre, this is not generally the case in Majorca. Additionally, the potential role of antibiotic consumption in each region was also analysed. Cumulative incidences in children under the age of 14 years were 26.6 per 100,000 child-years in Navarre (121.1 in children <2 years of age) and 7.3 per 100,000 child-years in Majorca (33.3 in children <2 years of age). In contrast, the incidences per 1,000 blood cultures were similar in both regions. The relative risks of occult bacteraemia, bacteraemic pneumonia and meningitis among the children of Navarre compared to Majorcan children were 11.8, 2.6 and 0.8, respectively. The risk for less virulent (vaccine serotypes plus 6A, 19A and 23A) and for more virulent serotypes (1 and 7) was 4.9 and 3.1 times higher in Navarre, respectively. The number of 7-valent pneumococcal conjugate vaccine (PCV7) doses administered between 2003 and 2004 were also higher in Navarre. Conversely, antibiotic resistance and paediatric prescriptions for broad-spectrum antibiotics were greater in Majorca. Although the most salient differences between both regions, including the effectiveness of pneumococcal conjugate vaccine in Navarre, appeared to be confounded by the higher frequency of blood cultures taken there, certain differences in serotype composition may be explained by the higher antibiotic consumption in Majorca.