Vancomycin relieves mycophenolate mofetil-induced gastrointestinal toxicity by eliminating gut bacterial ß-glucuronidase activity.

Mycophenolate mofetil (MMF) is commonly prescribed and has proven advantages over other immunosuppressive drugs. However, frequent gastrointestinal side effects through an unknown mechanism limit its use. We have found that consumption of MMF alters the composition of the gut microbiota, selecting for bacteria expressing the enzyme ß-glucuronidase (GUS) and leading to an up-regulation of GUS activity in the gut of mice and symptomatic humans. In the mouse, vancomycin eliminated GUS-expressing bacteria and prevented MMF-induced weight loss and colonic inflammation. Our work provides a mechanism for the toxicity associated with MMF and a future direction for the development of therapeutics.

Insights from community case management data in six sub-Saharan African countries.

There is strong research evidence that community case management (CCM) programs can significantly reduce mortality. There is less evidence, however, on how to implement CCM effectively either from research or regular program data. We analyzed monitoring data from CCM programs supported by the International Rescue Committee (IRC), covering over 2 million treatments provided from 2004 to 2011 in six countries by 12,181 community health workers (CHWs). Our analysis yielded several findings of direct relevance to planners and managers. CCM programs seem to increase access to treatment, although diarrhea coverage remains low. In one country, the size of the catchment area was correlated with use, and increased supervision was temporally and strongly associated with improved quality. Planners should use routine data to guide CCM program planning. Programs should treat all three conditions from the outset. Other priorities should include use of diarrhea treatment and insurance of adequate supervision.