The Alexander Project was established in 1992 to examine antimicrobial susceptibilities of bacterial isolates from community-acquired infections of the lower respiratory tract. Testing of a range of compounds was undertaken in a central laboratory. From 1992 to 1995, isolates were collected from geographically separated areas in countries in the European Union and various states in the USA. In 1996, the study was extended to include centres in Mexico, Brazil, Saudi Arabia, South Africa, Hong Kong and other European countries not included previously. Data generated by the project during 1996-1997 confirm France and Spain as European centres with high rates of resistance to penicillin among isolates of Streptococcus pneumoniae. Both intermediate (MIC 0. 12-1 mg/L) and resistant (MIC 2 mg/L) phenotypes are present. Combined resistance rates (intermediate and resistant) were >/=50% in 1997. Combined resistance rates in excess of 20% were found in the Republic of Ireland, Portugal, the Slovak Republic and Hungary. Penicillin resistance continues to evolve in the USA, with combined resistance rates of 16.4% (1996) and 18.6% (1997). In the new, non-European centres, e.g. Mexico and, in particular, Hong Kong (where resistant strains accounted for 50% of all isolates of S. pneumoniae in 1996 and 55.5% in 1997), there are centres where rates of resistance are high. Macrolide resistance is increasing generally among both penicillin-resistant and penicillin-susceptible isolates of S. pneumoniae. There is variation between countries, and in four out of the 16 centres for which both 1996 and 1997 data are available, rates of macrolide resistance have fallen. Overall, the percentage of S. pneumoniae strains that is resistant to macrolides exceeds the percentage that is resistant to penicillin. In 1996, 16. 5% of all S. pneumoniae isolates were resistant to macrolides compared with 10.4% resistant to penicillin, and in 1997 respective rates were 21.9% and 14.1%. beta-Lactamase production was the principal mechanism of resistance observed among isolates of Haemophilus influenzae. However, considerable variation in the percentage of isolates producing beta-lactamase (0-37.1%) was observed within this species. Within Europe, in the Republic of Ireland, France and Belgium, more than 15% of isolates were beta-lactamase producers. In Spain rates were as high as 31.7%. Outside Europe and the USA high rates were described in Mexico (25%), Saudi Arabia (27.9%, 16.7%) and Hong Kong (37.1%, 28.9%). Of H. influenzae from the USA, 30.4% were beta-lactamase producers in 1996 and 23.3% in 1997. beta-Lactamase production among isolates of Moraxella catarrhalis was observed in >90% of the isolates tested in 1996 and 1997.

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The Alexander Project is a unique, international, collaborative antimicrobial susceptibility surveillance study of bacterial pathogens causing community-acquired lower respiratory tract infection. Fifteen centres, ten in the European Union (EU) and five in the USA, each submitted up to 400 isolated per year for 2 years (1992 and 1993) to a central laboratory for re-identification and determination of MICs of 15 antimicrobials using the Sensititre microbroth incorporation technique. Of the total of 6385 isolates collected, Haemophilus influenzae (2718), Streptococcus pneumoniae (1856) and Moraxella catarrhalis (818) were the most frequently identified pathogens. Staphylococcus aureus (690). Haemophilus parainfluenzae (183) and Klebsiella pneumoniae (120) were identified less commonly. High-level penicillin resistance in S. pneumoniae (MIC > or = 2 mg/L) was found in 222 isolates, an overall prevalence of 12% which varied from < 1% in Germany, Italy, UK and two of the five USA centres, to 3.8-40.4% in the remainder, with the highest prevalence found in France and Spain. Intermediate penicillin resistance (MIC 0.12-1 mg/L) was identified in 228 isolates of S. pneumoniae, an overall prevalence of 12.3%, with individual centre prevalence varying widely (EU, 0-52.3%; USA, 0-20.9%) and not always following that of high-level resistance. Resistance to other, unrelated, antimicrobials, except notably the fluoroquinolones, was strongly associated with beta-lactam resistance. beta-lactamase production was detected in 492 isolates of H. influenzae, an overall prevalence of 18.1%. Rates of detection varied widely between centres from 1.4% in Weingarten, Germany in 1993 to 38.5% in Barcelona, Spain in 1992. In general, the prevalence of beta-lactamase production was higher and less variable in USA centres than in those of the EU. beta-Lactamase was detected consistently in the majority of isolates of M. catarrhalis with an overall prevalence of 81.7%. Virtually no other resistance phenotype was recognised in this species. Of the 690 collected, most isolates of S. aureus produced beta-lactamase with rates of detection varying from 52.2%-89.1%. Isolates from two centres, Genoa, Italy in 1992 and Paris, France in 1993, were associated with a high prevalence of methicillin-resistance (34.8% and 43.8%, respectively). Combined isolates of H. parainfluenzae and K. pneumoniae accounted for only 4.7% of the total collection. Although the current data are insufficient to allow analysis of trends in resistance, the study participants have continued to collect further isolates in 1994 and 1995 which will be reported in the future.

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