Surveillance study of the susceptibility of Haemophilus influenzae to various antibacterial agents in Europe and Canada

Background: Haemophilus influenzae is a major respiratory tract pathogen that is becoming increasingly resistant to beta-lactam antibiotics. Materials and methods: Using a microdilution method performed to Clinical and Laboratory Standards Institute (CLSI) guidelines, we determined the minimal inhibitory concentrations (MICs) of various antibacterial agents against 536 isolates of H. influenzae. The isolates were obtained from patients with respiratory tract infections being treated in 18 European and two Canadian centres between 2006 and 2007. Results: Levofloxacin, moxifloxacin, cefixime and cefpodoxime with MIC90 values of <= 0.03, <= 0.03, 0.03 and 0.06 mu g/mL, respectively, were the four most active agents tested. Overall, amoxicillin resistance was observed in 25.0% of the strains, but was generally reversed with the addition of clavulanic acid. In 73 strains (13.6%) resistance was due to beta-lactamase (BL) production while the remainder (n - 61; 11.4%) were BL-negative, amoxicillin-resistant (BLNAR) strains. Comparison of penicillin binding protein 3B sequences in BLNAR isolates revealed that only mutations at amino acids 502 (alanine [Ala] -> threonine [Thr]/valine [Val]) and 526 (asparagine [Asn] -> lysine [Lys]) were significantly associated with amoxicillin resistance among European H. influenzae isolates (p < 0.0001 for both). Conclusions: This surveillance study highlights an increased prevalence of amoxicillin-resistant strains of H. influenzae compared with a previous study that we performed in 2004/2005. The third-generation cephalosporins cefixime and cefpodoxime, as well as amoxicillin plus clavulanic acid, continue to be very active against both BL-positive and BLNAR strains of H. influenzae, and thus remain useful treatment options for patients with respiratory tract infections.