Nicotinamide, otherwise known as vitamin B3, enhances the killing of Staph. aureus in mice:
In a systemic murine infection model as well as in murine and human peripheral blood, nicotinamide enhanced killing of S. aureus by up to 1,000 fold but had no effect when administered to either C/EBPε-deficient mice or mice depleted of neutrophils. Nicotinamide was efficacious in both prophylactic and therapeutic settings. Our findings suggest that C/EBPε is an important target to boost killing of bacteria by the innate immune system.
Later in the paper, the authors discuss whether nicotinamide could be given safely to humans in the proper (high) doses.
An important concern that arises from the study is whether the therapeutic effect documented with S. aureus could be achieved in human subjects using safe NAM doses. In human trials, NAM is frequently administered as a modifier to patients undergoing radiotherapy (47, 48, 57, 58). In these trials, a plasma concentration of 1 mM NAM is routinely achieved, a concentration that we used in our peripheral whole blood killing assays to demonstrate NAM efficacy. Therefore, our data suggest that a NAM concentration safely achievable in humans could provide protection against S. aureus infection.
One reason this is so important is because of bacterial resistance to antibiotics.
Our finding that NAM has an important effect on immune-mediated killing of S. aureus in mouse and in human blood has a number of additional therapeutic implications. In an age when the number of antibiotics in the pipeline is limited and development of resistance occurs rapidly, use of complementary strategies to antibiotic treatment would provide a method of limiting development of antibiotic resistance. Because C/EBPε is a transcriptional activator of a number of important antimicrobial factors, induction of resistance to multiple host factors is less likely. Likewise, the use of an immune boosting strategy coupled with conventional antibiotics could provide important synergy.
Coinfection with Mycobacterium tuberculosis and human immunodeficiency virus (HIV) is responsible for one-third of all deaths due to acquired immunodeficiency syndrome. More than 99% of cases of HIV-M. tuberculosis coinfection occur in the developing world, where limited resources add urgency to the search for effective and affordable therapies. Although antimicrobial agents against each of these infections are available, single agents that have activity against both M. tuberculosis and HIV are uncommon. The activity of nicotinamide has been evaluated in 2 different eras: in anti-M. tuberculosis studies performed during 1945-1961 and in anti-HIV studies performed from 1991 to the present. This review brings together these 2 bodies of inquiry and raises the possibility that, with more study, this small molecule could emerge at the beginning of the 21st century either as a therapeutic agent in itself or as the lead compound for a new class of agents with activity against both M. tuberculosis and HIV.