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Posaconazole demonstrates efficacy as prophylaxis against IFI in high-risk neutropenic Chinese patients and is well tolerated during long-term use (ClinicalTrials. gov number, NCT00811928).

Increasing the specificity of chemotherapy may improve the efficacy of cancer treatment. Toward this aim, we developed a strain of bacteria to express enzymes for selective prodrug activation and non-invasive imaging in tumors. b-glucuronidase and the luxCDABE gene cluster were expressed in the DH5a strain of Escherichia coli to generate DH5a-lux/bG. These bacteria emitted light for imaging and hydrolyzed the glucuronide prodrug 9ACG to the topoisomerase I inhibitor 9-aminocamptothecin (9AC). By optical imaging, colony-forming units (CFUs) and staining for bG activity, we found that DH5a-lux/bG preferentially localized and replicated within CL1-5 human lung tumors in mice. The intensity of luminescence, CFU and bG activity increased with time, indicating bacterial replication occurred in tumors. In comparison with DH5a-lux/bG, 9AC or 9ACG treatment, combined systemic administration of DH5a-lux/bG followed by 9ACG prodrug treatment significantly (Po0.005) delayed the growth of CL1-5 tumors. Our results demonstrate that prodrug-activating bacteria may be useful for selective cancer chemotherapy.

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