Ten years of Hib vaccination in Italy: prevalence of non-encapsulated Haemophilus influenzae among invasive isolates and the possible impact on antibiotic resistance.

The introduction of Haemophilus influenzae type b (Hib) conjugate vaccines has greatly reduced the incidence of invasive Hib disease. However, concern exists about the possible emergence of "strain replacement". We report the epidemiology and characterization of isolates from invasive H. influenzae disease in Italy through 2007-2009, 10 years after Hib vaccination was introduced. Invasive H. influenzae disease cases were detected through the National Surveillance of Invasive Bacterial Disease. Seventy-eight H. influenzae strains were serotyped and tested for antimicrobial susceptibility. Genetic basis of resistance to β-lactams was investigated. The annual incidence of invasive H. influenzae infection was 0.06/100,000 in 2007, 0.08/100,000 in 2008 and 0.09/100,000 in 2009 in all age groups. A slight increase in disease incidence has been observed in adults ≥65 years since 2007. Nonencapsulated (ncHi) predominated among H. influenzae isolates from all age groups: 61.5%, 76.0%, and 75.0% for <5, 5-64 and ≥65 years, respectively. Although ncHi mainly caused bacteremia, meningitis due to ncHi increased in comparison with previous data (38.6% in 2007-2009 vs. 26.2% 1997-2002). Prevalence of encapsulated non-Hib strains grew significantly (4.1% in 1997-2002 vs.16.7% in 2007-2009; p<0.001), although they remained rare. Resistance to ampicillin mediated by β-lactamase declined, but that due to altered penicillin-binding protein 3 increased. In conclusion, routine use of Hib vaccines produced both a drastic decrease in the number of invasive H. influenzae cases and epidemiological changes in disease. Overall, pediatric H. influenzae disease has become less common whereas there has been a slight increase of disease in the elderly. A marked change in the predominant serotype from Hib to ncHi has occurred. Changes in the H. influenzae population moderately affected antibiotic resistance trends.