The Alexander Project: using in-vitro susceptibility data for choosing empirical therapy in LRTI

An international collaborative survey of susceptibility in community-acquired lower respiratory tract infection pathogens collected > 6000 strains from six countries during 1992 and 1993. The four major pathogens were Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus. MICs of 15 antibiotics were determined and sensitivity interpretations applied using breakpoints based on those of the NCCLS. This analysis highlighted some anomalies, notably for beta-lactams against S. pneumoniae and macrolides against H. influenzae, where apparent sensitivity proportions did not accord with the distribution of MICs. Further analyses were undertaken in order to rank the antibiotics in order of potential usefulness for empirical treatment of LRTI: these included in-vitro potency (mode MIC and MIC90) and a pharmacodynamic comparison, using the ratio Cmax (free drug): MIC90. According to study breakpoints, the most active agents overall were, for S. pneumoniae, cefuroxime, clarithromycin, ofloxacin and chloramphenicol; for H. influenzae, azithromycin, amoxycillin/ clavulanate, cefixime, ceftriaxone, quinolones and doxycycline. However, other analyses suggested that the most active agents overall were, for S. pneumoniae, amoxycillin (+/- clavulanate) and ceftriaxone, and, for H. influenzae, quinolones, ceftriaxone, cefixime and amoxycillin/clavulanate. Overall, the antimicrobial agents with the greatest potential usefulness for empirical treatment were amoxycillin/ clavulanate, ceftriaxone, cefuroxime, ofloxacin and co-trimoxazole. The choice of empirical therapy depends upon local epidemiology and clinician choice, but the Project data may be of value in the decision-making process.