Changes in antibiotic resistance rates of invasive Haemophilus influenzae isolates in England and Wales over the last 20 years

Objectives: The aim of this study was to determine trends in antibiotic resistance profiles of invasive clinical Haemophilus influenzae isolates over the last 20 years. Methods: Microbiology laboratories throughout England and Wales regularly submit invasive H. influenzae isolates to the Health Protection Agency for serotyping and antimicrobial susceptibility testing. Antimicrobial resistance was defined using the British Society for Antimicrobial Chemotherapy criteria (http://bsac.org.uk). All H. influenzae isolates from blood and cerebrospinal fluid (CSF) cultures between January 1985 and December 2004 were included. Results: Over the20 year study period, 6805 H. influenzae isolates from blood (n = 4932, 72.5%) and CSF (n = 1873, 27.5%) were obtained. Over half the isolates (3736/6805, 54.9%) were identified as Hib, 38.9% (n = 2644) as non-capsulated and 6.2% (n = 425) as other capsulated serotypes. Resistance to ampicillin was highest at 16.2%, followed by trimethoprim (7.7%), tetracycline (1.8%) and chloramphenicol (1.2%). All isolates were susceptible to cefotaxime and only four (0.06%) were resistant to rifampicin. When analysing trends, chloramphenicol and tetracycline resistance rates have remained low since the late 1980s. Ampicillin resistance increased slowly until the mid-1990s and then gradually declined to its lowest rate of 11.6% in 2004. Resistance to trimethoprim initially fell from 10% in 1985 to 1.8% in 1989, but has continued to rise since then to 11.9% in 2004. In a logistic regression model, year of isolate (P < 0.001), non-capsulated H. influenzae (P < 0.001) and younger age (P = 0.004) remained independently associated with trimethoprim resistance. Conclusions: Rifampicin and cefotaxime remain highly effective against all invasive H. influenzae isolates. Resistance to ampicillin, chloramphenicol and tetracycline has declined over the past 10 years, but trimethoprim resistance continues to increase rapidly. This finding requires further study but may reflect increased use of trimethoprim in the childhood population.