Does pre-treatment with lamivudine prime for adefovir resistance of hepatitis B virus infection?

My recent leading article on silver-based products as antimicrobial agents was intended primarily to address microbiological issues such as bacterial susceptibility and the potential for the development of resistance to these products. Consequently, I did not consider the toxicological issues raised by Bayston et al. in their comment upon my article. Obviously, a heavy-metal cation such as silver has the potential to inhibit processes in mammalian cells and as noted by Bayston et al., various forms of silver-associated toxicity have been reported, although fortunately they are rare in clinical practice. Experience with antibiotics tells us that dosing with sub-MIC levels creates conditions favourable for the selection of resistant organisms. Applying these principles to the silver situation led me to conclude that products releasing high levels of silver were unlikely to generate conditions for the selection of silver-resistant microorganisms. However, I agree with Bayston et al. that the use of such products could pose a greater risk of toxicity than low silver release formulations and that the therapeutic index for silver-based products may be rather low. Concerning the issue of zones of inhibition raised by Bayston et al., it may well be true that free silver ions capable of diffusion are not released from nanoparticle systems. Unfortunately, the abstract, cited by Bayston et al., does not appear to support this claim. No zones of microbial inhibition were observed with the silver-impregnated catheters used by the authors, implying no diffusion of free silver ions from the catheter material. However, there appeared to be insufficient silver in this product even to affect the viability of bacteria (Staphylococcus epidermidis) bound to the catheter surface. Consequently, it is difficult for Bayston et al. to argue from these data that organisms attached to the surface of the catheter can be killed by silver in the absence of diffusion of the cation from the device.