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**21** 

Martin Sedlacek

*Lebanon* 

**Nontraditional Anti - Infectious** 

*Dartmouth Hitchcock Medical Center, One Medical Center Drive* 

The distinction between antibiotic and non antibiotic medications is in fact quite arbitrary as drugs against bacteria can have unpredictable side effects in man and drugs developed for use in humans can affect microbes. It would be extremely surprising if it was otherwise, as eukaryotes and prokaryotes are related by evolution and share conserved molecular mechanisms. Many antibiotic and non antibiotic medications have closely related

For example, both antimicrobial activity and an affinity for brain tissue of the phenothiazine compound methylene blue were described by Paul Ehrlich in the 19th century. Early uses of phenothiazines included treatment of urinary tract infection and postoperative analgesia. As a positive effect on psychotic patients was discovered, phenothiazines became with the development of chlorpromazine an important tool in psychiatry (Williams, 1995). With the discovery of penicillin the antimicrobial activities of phenothiazines and other earlier compounds fell into the background, but with the emergent problem of antibiotic resistance in more recent years there was new interest. Phenothiazines have activity against multidrug resistant *Staphylococcus aureus* and *Enterococcus faecalis*, presumably through the inhibition of

As a routine, antibiotic medications are tested for their effects on the eukaryotic host as these constitute potential side effects. While the ideal antibiotic would have no side effects at all, the discovery of unexpected side effects has lead to important drug developments. For instance, the clinical observation of a hypoglycemic effect of sulfonamide antibiotics led to the development of sulfonylureas for the treatment of diabetes. Likewise the observation that Sulfanilamide causes hens to lay eggs without shells because of alkaline diuresis led to the development of acetazolamide and ultimately the thiazide diuretics. The initial observation derived from the similarity between the sulfonamide ion and the bicarbonate ion. The antiviral amantadine was found to be useful in the treatment of Parkinson's disease and motility agents to treat gastroparesis are derived from the observation of the bothersome gastrointestinal side effects of erythromycin. As described below, even Lipitor, the "best selling drug in the world" with \$11 Billion of annual sales according to Forbes magazine, was developed from a compound initially discovered as an antibiotic originating

On the other hand side, the efforts to look into the unintended effects on microbes of non antibiotic medications have been less systematic. Non antibiotic medications can affect

**1. Introduction** 

from a fungal broth.

chemistries and share the same historic roots.

bacterial efflux pumps (Kristiansen J.E. et al., 2007).

**Agents in Hemodialysis** 

