Epidemiology and evolution of antibiotic resistance of Haemophilus influenzae in children 5 years of age or less in France, 2001-2008: a retrospective database analysis.

Trends in the evolution of antimicrobial resistance and mechanisms of resistance of Haemophilus influenzae to β-lactam antibiotics in France were assessed through a retrospective database review. The antimicrobial resistance of 2,206 H. influenzae strains from children aged ≤5 years was studied between 2001 and 2008. Strains were isolated from blood or cerebrospinal fluid (n = 170), bronchial secretions (n = 188), middle ear fluid, and nasopharynx or conjunctiva (n = 1,848). A proportion of 95.1 % (n = 2,097) were non-typeable H. influenzae (NTHi). β-lactamase production was identified in 27.5 % of NTHi isolates (all TEM-1), while β-lactamase-negative ampicillin resistance and β-lactamase-negative amoxicillin-clavulanate resistance among NTHi was 16.9 and 6.4 %, respectively. Over time, a statistically significant decrease in β-lactamase-producing strain prevalence (p < 0.0001) and a statistically significant increase in β-lactamase-negative ampicillin-resistant (BLNAR) strains (p < 0.0001) were observed in NTHi isolates from 2001 to 2008. The largest changes coincided with a campaign to reduce antibiotic use in France. An increasing diversity of amino acid substitution patterns was observed, with the emergence of group III/'III-like' patterns linked to high-level resistance. In France, amino acid substitution patterns are increasingly diverse, and strains with high-level antibiotic resistance are emerging. This study highlights the complexity of resistance dynamics within a given country. These results have implications on antibiotic guidelines and illustrate the importance of continued surveillance.