In the meantime, I found yet another gem. Here is a python script that sends a signal to somescript whenever there is any mouse or keyboard activity:

from pynput import keyboard
from pynput import mouse
import os

def send_signal()
        os.system('pkill -USR1 somescript')

def on_press(key): 
	send_signal()

def on_move(x, y):
	send_signal()

def on_click(x, y, button, pressed):
	send_signal()

def on_scroll(x, y, dx, dy):
	send_signal()

with mouse.Listener(on_move=on_move, on_click=on_click, on_scroll=on_scroll) as listener:
	with keyboard.Listener(on_press=on_press) as listener:
		listener.join()

It would be easy to adapt the above to only send the signal in a subset of cases (e.g., only on left clicks).

I tried it and it worked like a charm. I just needed to install libxss-dev (provides scrnsaver.h) before compiling.

I found a solution. It requires that python3 and the pyuserinput module (which contains pymouse) be installed.

#!/usr/bin/python3
from pymouse import PyMouseEvent
import os
class ClickDetector(PyMouseEvent):
    def __init__(self):
        PyMouseEvent.__init__(self)
    def click(self, x, y, button, press):
        '''Send signal when left click is pressed.'''
        if button == 1:
            if press:
                os.system('pkill -USR1 somescript')
ClickDetector().run()

If the above is running in the background, my mouse works normally and any time I left-click on anything a SIGUSR1 is sent to somescript.

Perhaps you can adapt the above and use it instead of xscreensaver for your purposes, although as-is it does not respond to keyboard input.

I tried both of these in my xbindkeys, but with them I lose the ability to use the mouse click altogether (i.e., I can move the mouse but nothing happens when I click on things):

"xdotool click 1; pkill -USR1 somescript"
  b:1 + release

"xvkbd -text "\m1"; pkill -USR1 somescript"
  b:1 + release

I tried adding a short delay to the command. Also tried just b:1 without "+ release". No luck with either.

Any ideas? I've been going around in circles with this. A CLI solution would be preferable.