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Haemophilus influenzae, a colonizer of the nasopharynx, in children causes mainly otitis and sinusitis. The primary objective of this study was to determine the prevalence of pharyngeal colonization by H. influenzae, and the secondary objectives were to identify risk factors associated with H. influenzae colonization and its antibiotic susceptibility.A prospective, multicenter study of nasopharyngeal carriers of H. influenzae was conducted in the pediatric consulting rooms of 10 primary healthcare centers in Murcia (Spain). The study consisted of 404 healthy children less than 5 years of age and was carried out during winter (January–March) and summer (July–September) of 2015. A nasopharyngeal sample was collected from each child, and an epidemiologic survey was completed by a pediatrician.In total, 112 (27.7%) children had colonization by H. influenzae, with 73.2% of cases in winter and 26.8% of cases in summer (P < 0.001). The median (interquartile range) age in months of the colonized children (13 months, 12–47.5) was lower than that of the noncolonized children (46 months, 12–49) (P < 0.001). All H. influenzae found were nontypeable H. influenzae (NTHi). Among 112 isolates, 20% were ampicillin resistant, of which 10% produced β-lactamase, and 9% were ampicillin resistant and did not produce β-lactamase. A logistic regression analysis showed that young age (odds ratio: 0.98) and the winter period (odds ratio: 3.41; P < 0.001) were risk factors for colonization by NTHi.Colonization by NTHi is high in this Mediterranean coast region with remarkable ampicillin resistant. Younger age and the winter period were facilitating factors.