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Also I find the multiple shot observations suspect. The reason for double taps (as invented by the OSS under Applegate and Fairbairn) was to address the failure rate of the 45 ACP hardball round to Stop. I have seen schools of shooting that teach dumping "a magazine full" into a burglar. You are legally responsible for every round you fire and dumping 15 rounds into the guy is going to make even the most sympathetic jury be tempted to find for murder.
22 ammo, even up to .223, has a record of failure that anyone serious about defense should find unacceptable. Read "BlackHawk Down" for some observations and frustrations of our sons in battle shooting the enemy 6 or 7 times without putting them down. Caliber plays an energy transfer role that is hard to define, yet impossible to ignore. For a discussion of different caliber vs Speed effects on various animals, see "African Rifle Cartridges" by Taylor.
The old timers used to say shoot up to the limit of what you can control. A 44 Special hollowpoint makes a good wife gun (about the same as the 45 but more reliable) or for bigger guys a 210 grain Silvertip .44 Mag should be sufficient. You may only get in one shot. If you feel that more that one shot is required, then up you power level. Get a shot in first, make it hit where you want it to, but spray and pray or multiple shot techniques, unless against armor, does not seem the right path in my humble opinion.