Right, I have some interesting updates for you;

The issue is indeed due to the usual Microsoft Patch Tuesday. I have removed KB4338815 and the problem has completely subsided on a few boxes.

Since the number of clients varies as you have described we now have a fully patched 2016 test machine running Xeams and we are watching this very carefully.

The 2012R2 servers are running fine being patched completely until JUNE 2018.  Attempting to install the security roll up KB4338815 from July will cause these problems.

We have also noticed that KB4054566 (update for .Net) is also causing general installation problems with many clients as is KB4054566 (New .Net 4.7.2)

Either way, removing the July security rollup KB4338815 will mitigate the SMTP binding problem so you can go ahead and inform those clients to start an uninstall.

My advice would be to firstly take a checkpoint if a VM or a backup if physical.

I'll be sure to update you on the 2016 boxes as soon as the config is complete.

Please also keep me updated on your side.

James.