THE ALEXANDER PROJECT - USING IN-VITRO SUSCEPTIBILITY DATA FOR CHOOSING EMPIRICAL THERAPY IN LRTI

An international collaborative survey of susceptibility in community-a cquired lower respiratory tract infection pathogens collected >6000 st rains from six countries during 1992 and 1993. The four major pathogen s were Streptococcus pneumoniae, Haemophilus influenzae, Moraxella cat arrhalis and Staphylococcus aureus. MICs of 15 antibiotics were determ ined and sensitivity interpretations applied using breakpoints based o n those of the NCCLS. This analysis highlighted some anomalies, notabl y for beta-lactams against S. pneumoniae and macrolides against H. inf luenzae, where apparent sensitivity proportions did not accord with th e distribution of MICs. Further analyses were undertaken in order to r ank the antibiotics in order of potential usefulness for empirical tre atment of LRTI: these included in-vitro potency (mode MIC and MIC(90)) and a pharmacodynamic comparison, using the ratio C-max (free drug): MIC(90). According to study breakpoints, the most active agents overal l were, for S. pneumoniae, cefuroxime, clarithromycin, ofloxacin and c hloramphenicol; for H. influenzae, azithromycin, amoxycillin/clavulana te, cefixime, ceftriaxone, quinolones and doxycycline. However, other analyses suggested that the most active agents overall were, for S. pn eumoniae, amoxycillin (+/- clavulanate) and ceftriaxone, and, for N. i nfluenzae, quinolones, ceftriaxone, cefixime and amoxycillin/clavulana te. Overall, the antimicrobial agents with the greatest potential usef ulness for empirical treatment were amoxycillin/clavulanate, ceftriaxo ne, 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.