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Patients with cystic fibrosis (CF) are often colonised with multiresistant organisms. In vitro data suggest that bactericidal activity may result from antibiotic synergy even if species are resistant to individual agents on routine resistance testing. Simultaneously testing the bactericidal activity of two or more antibiotics (multiple combination bactericidal antibiotic testing, MCBT) is one approach that has been suggested to combat this problem.
This multicentre, prospective, double blind, randomised controlled trial investigated the in vivo effects of selecting antibiotics for exacerbations of CF, based on MCBT versus conventional sensitivity testing. Sputum was tested every 3 months for up to 4 years from 251 patients with CF over 12 years of age who were chronically infected with multiresistant organisms. Both testing methods were used for each sample. Using the results, combinations of two antibiotics with or without nebulised tobramycin were recommended by two separate investigators—one using the MCBT results and the other the conventional sensitivity results.
One hundred and thirty two patients developed exacerbations and were randomised; 64 received MCBT directed therapy and 68 conventionally guided therapy. The primary end point was time to the next exacerbation and secondary end points were changes in sputum bacteria density, FEV1, FVC, dyspnoea, white cell count, C reactive protein and erythrocyte sedimentation rate, and length of hospital stay. There was no difference in the primary end point between the two groups (85 days in the MCBT group v 79 days in the conventional group). The reduction in white cell count was greater in the MCBT group (p = 0.02) but hospital stay was 3 days longer (p = 0.03). Otherwise, no significant differences were observed.
Caution must be taken when judging the value of tests which appear useful in vitro: this may not necessarily translate to clinical benefit.