I'm looking into using W3 Total Cache on my multi-site installation, but that would mean that I have to give up on database sharding (I'm using HyperDB, but Multi-DB is the same basic idea). I expect my realistic cap on sites is about 4000-5000, with 8000 being the hard cap (I'll never go above 8000 sites). At ~15-20 tables per site (depending on installed plugins), that means I'm looking at potentially 60,000 to as many as 160,000 tables. MySQL can easily handle that number (I believe the max is in the billions), but I'm not sure what kind of performance issues I might run into (ignoring hardware—I can add lots of RAM if necessary).
Is anyone running a multi-site installation of this size on just one database (or something nearly that size)? How's it working for you?
I'm also looking into the mysqlnd_ms database extension, that handles sharding or master/slave replication at the driver level, meaning that Wordpress never needs to know. Anyone have experience with that extension?