More Refs on Antifungals w/ Antibacterial Effects

[Guest guest]

I gave one Pub Med reference for Fluconazole increasing immune cell

bacterocidal activity, a possibly overlooked mechanism as many drugs

including minocycline (see previous post) and ceftriaxone

(references to come) upregulate host immune defenses independently

of any direct effect on pathogens.

Here's two more refs:

Ref 1 echoes the one I gave before, about Fluconazole enhancing

bacterocidal activity of PMN's (polymorphonuclear neutrophils), and

could well be the source paper for that:

Fluconazole increases bactericidal activity of neutrophils through

non--cytokine-mediated pathway.

Zervos EE, Fink GW, Norman JG, Robson MC, Rosemurgy AS.

Department of Surgery, University of South Florida, Tampa, USA.

BACKGROUND: Polymorphonuclear neutrophils (PMNs) preincubated with

fluconazole (FCZ) demonstrate enhanced bactericidal activity in

vitro. OBJECTIVE: This study was undertaken to determine the role of

cytokines in FCZ-induced augmentation of PMN function.

METHODS: PMNs were preincubated with PBS or FCZ and exposed to

Escherichia coli. Cell culture supernatants and mRNA were isolated

after preincubation and again after exposure to E. coli. Tumor

necrosis factor-alpha, interleukin (IL)-1 beta, and IL-8 protein and

mRNA levels were determined using enzyme-linked immunosorbent assay

and polymerase chain reaction, respectively. Results were compared

using the Student's t test.

RESULTS: Preincubation of PMNs with FCZ resulted in enhanced killing

but no difference in cytokine protein or mRNA levels when compared

to control. After exposure to E. coli, PMNs significantly up-

regulate IL-8 and tumor necrosis factor-alpha independent of the

solution with which they were preincubated.

CONCLUSIONS: Up-regulation of the cytokine cascade plays a minor

role, at most, in the mechanism through which FCZ augments the

bactericidal activity of PMNs.

PMID: 8810964 [PubMed - indexed for MEDLINE]

This next reference is interesting because it's talking about the

same mechanism I think Jaep has in mind for azoles acting

against CWD, by interfering with sterol synthesis that maintains the

membranes of these beasties. But note: the one azole that had NO

efficacy against this particular mycobacterium was Fluconazole.

Bactericidal and inhibitory effects of azole antifungal compounds on

Mycobacterium smegmatis.

CJ, Lamb DC, DE, SL.

Institute of Biological Sciences, University of Wales Aberystwyth,

SY23 3DA, Aberystwyth, UK.

Azole antifungals are central to therapy and act by inhibiting a

cytochrome P450, sterol 14-demethylase and blocking normal sterol

synthesis. Our recent identification of a mycobacterial sterol

biosynthetic pathway led us to probe the efficacy of a range of

these compounds against Mycobacterium smegmatis. Several showed

equivalent or greater inhibitory effects to those against Candida

albicans, and bactericidal activity was demonstrated for four

compounds, clotrimazole, econazole, miconazole and tebuconazole. The

major drug used clinically, fluconazole, was ineffective. The

results are discussed in the light of the world-wide spread of

tuberculosis, including drug-resistant forms and the requirement for

new drugs.

PMID: 11064188 [PubMed - indexed for MEDLINE]