The Alexander Project: the benefits from a decade of surveillance.

The Alexander Project, initiated in 1992 as an international, multicentre, longitudinal surveillance study of antimicrobial susceptibility among common respiratory pathogens, has been pivotal in defining the role of global surveillance. At the time, there were few studies in which data were collected in a way that allowed meaningful comparisons to be made between studies, locations or over time. The project instituted the use of a central laboratory and standardized methods for the collection of isolates and determination of susceptibility, and this was continued with the addition of two further reference laboratories. Data from the study have provided a resource for measuring trends in the susceptibility patterns of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis at country, regional and global levels. Determination and publication of quantitative MICs enabled detailed assessment of changes in susceptibility distributions and assessment of microbiological and potential clinical susceptibility using different breakpoints, including those based on pharmacokinetic/pharmacodynamic parameters. Comparisons of antimicrobial usage patterns and resistance prevalences over time allowed hypotheses to be examined with respect to the role of quantity and type of antimicrobial use in the selection and spread of resistance. The resulting collection of isolates has provided a valuable resource for molecular studies into the evolution of resistance over time and location; a substantial proportion of this collection is now in the public domain. This paper reviews the 10 years of the Alexander Project and the benefits it has brought to an understanding of the evolution of antibacterial resistance in community respiratory bacteria.

The Alexander Project 1998-2000: susceptibility of pathogens isolated from community-acquired respiratory tract infection to commonly used antimicrobial agents.

OBJECTIVES: The Alexander Project is a continuing surveillance study, begun in 1992, examining the susceptibility of pathogens involved in adult community-acquired respiratory tract infections (CARTI) to a range of antimicrobial agents. MATERIALS AND METHODS: This study tested the susceptibility of isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis collected between 1998 and 2000 to 23 antimicrobials. Minimum inhibitory concentrations of agents were determined using the broth microdilution method and interpreted according to NCCLS and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. RESULTS: In total, 8882 isolates of S. pneumoniae, 8523 isolates of H. influenzae and 874 isolates of M. catarrhalis were collected during 1998-2000 from centres in 26 countries. The world-wide prevalence of penicillin resistance (penicillin MICs > or = 2 mg/l) in isolates of S. pneumoniae was 18.2% over the study period, and the prevalence of macrolide resistance (erythromycin MICs > or = 1 mg/l) in this pathogen was 24.6%. Over the study period, macrolide resistance exceeded penicillin resistance in 19 of the 26 countries included in the study. Of the non-fluoroquinolone agents, the only oral agents to which over 90% of S. pneumoniae isolates were susceptible at both NCCLS and PK/PD breakpoints were amoxicillin (95.1%) and co-amoxiclav (95.5-97.9%). The prevalence of fluoroquinolone-resistant S. pneumoniae (ofloxacin MICs > or = 8 mg/l) was 1.1%. Gemifloxacin was the most potent fluoroquinolone tested against S. pneumoniae (99.9% susceptible). In isolates of H. influenzae, beta-lactamase production was 16.9%, whereas the prevalence of beta-lactamase-negative, ampicillin-resistant strains was low (0.2%). beta-Lactamase production in M. catarrhalis world-wide remained high over the period studied (92.1%). Using PK/PD breakpoints, the most active non-fluoroquinolone agents against H. influenzae were ceftriaxone (100% susceptible), cefixime (99.8%) and co-amoxiclav (98.1-99.6%). Co-amoxiclav, cefdinir and cefixime (100%) were the most active beta-lactams against M. catarrhalis. Both H. influenzae and M. catarrhalis were highly susceptible to the fluoroquinolones. CONCLUSIONS: These data demonstrate the continued evolution of and geographical variation in bacterial resistance and highlight the need for appropriate prescribing of antimicrobials in CARTI, using agents with adequate activity, based on local susceptibility profiles and PK/PD parameters.