For what its worth, over the last 20 of reading the NRA 'armed citizen', I guess I've read of a couple of dozen fatal resident-on-perp shootings in HD situations in which a 22 'revolver' was used. There are a lot of variables determining the fatal outcome I'm sure, but for what its worth.....
Also, remember a .25 or .380 JHP may be a good compromise as far as lethality vs earsaving, relative to earsplitters like 357 or 45.

I could see a .22lr revolver, that gets rid of the reliability issues for the most part - as long as you are using quality .22lr ammo.

If noise is your biggest concern, I wouldn't worry about it.  First, I really wouldn't recommend a less-effective lifesaving tool; defending your life is much more important than protecting your hearing.  Second, a few gunshots aren't going to be that big of a deal.  Some folks seem to be convinced that firing a gun indoors without hearing protection will leave you looking like a bystander at the bombing of a discotheque, with blood running out your ears and instant stone deafness.  I've fired quite a few guns over the years without the benefit of hearing protection, such as when hunting, and my annual audiograms keep coming back satisfactory.  If the internet rumors about hearing loss had merit, everyone who was ever a bit slow getting their earmuffs back on after a cease-fire at the range would be learning American Sign Language right now.

The “mouse gun” calibers (.22, .25 and .32), while easy to carry, have a very high failure rate as compared to the larger caliber cartridges. If the criminal is likely to be affected by a psychological stop (“Hey, I’m tired of getting shot, so I’ll stop.”), these rounds are as good as any others. I believe that’s why they compare favorably to the larger calibers in the statistic regarding the percentage of people stopped with one shot. Those are likely psychological stops rather than physical incapacitations.

While I agree any gun is better than no gun, I can’t advise you to carry pistols under .35 caliber. They work any many cases, but if you do happen to encounter a motivated attacker, they are far more likely to fail.

http://americanhandgunner.com/defensive-carry/

I am not here to say that the 22LR is the best.
All I am saying and probably many others feel the same way, like the Mossad, and other countries that there is a place for the 22LR in defensive operations as well as offensive.
It is lethal as “Iraqi vet” showed in the video much further than one can shoot accurate with the .22LR at least to 440 yrds by military standards.


http://www.tactical-life.com/tactical-weapons/israeli-mossad-22-lrs/
Israeli Mossad .22 LRS
An enemy of Israel believes that he has successfully slipped away from the Mossad after his heinous act of terrorism. It’s a beautiful evening and time for a stroll. As the terrorist steps out of his apartment his chest is peppered with a handful of .22 Long Rifle bullets that immediately end his terrorist career. The only thing that the local police find is a dead terrorist and a small pile of .22 LR brass casings sprinkled close to the deceased.


http://www.onwardoverland.com/austday/skymarshals2.html
Air Marshals in Training
Israeli air marshals, among the first deployed, carried Beretta .22 autoloaders, relying on precise shot placement and multiple hits to eliminate a threat. It should be noted, too, that the Israelis carried their Berettas with the chamber empty and were trained to rack the slide as they brought the pistol into action.
At least some of the Jordanian air marshals have been equipped with suppressed .22 pistols.



http://filmcriticsunited.com/22bullets.html
22 Bullets
And if you shoot a guy 22 times maybe somebody should’ve thought of shooting him in the head.  Charly shoots people in the head.

Israeli assassins looking for a quiet tool to carry out wet work and air marshals trying to minimize the risk of damaging an airplane are apples and oranges compared to home defense.

I feel the biggest caliber that a homeowner can comfortable fire multiple shots in succession with is what should be used by any given person. At this point in time, the only thing my 110 lbs wife can fire comfortably is her mosquito. She is isn't yet comfortable shooting anything bigger so if she is not even comfortable shooting a .40 or my 10mm at the range under calm, controlled circumstances, I don't think I'd want her trying to use it in a real in home situation. I'd much rather her use what she is most comfortable with at this time. I'd rather her be confident with a smaller gun than shaky and uncomfortable with a larger caliber. Obviously .22 lr isn't the best self defense round, but I'd rather her get 1,2, or 3 rounds of .22 in a perp than zero with a 40 cal.

You are correct.

Any gun is better than no gun.

Being able to fire accurate shots with the largest caliber you can reliably do it with is the most important aspect of using a firearm for HD.

In your wife's case, a 22lr might be the best choice.

Does anyone have a .22lr pistol that they feel is on the same level of reliability as say, their glock, m&p or other standard polymer pistol?

For now it is, but just as all things, with a little more practice I think she can become more comfortable with a bigger caliber and then I will feel better about her home defense options when I am not present. 

A pistol caliber carbine would be perfect for her.

My wife is small bit she shoots my Ruger PC9 extremely well.

Ita a 9mm carbine that takes pistol magazines (Ruger P series)

Here's a video of some kid shooting one


If you can find them, they're a great little carbine.
I found one a couple years back at a gun show.

Does anyone have a .22lr pistol that they feel is on the same level of reliability as say, their glock, m&p or other standard polymer pistol?