Like Dojo mentioned, I haven't encountered any tool that's 100% effective. From my experience, Combofix fix seems to be pretty good at handling rootkits, but while it's simple to use, it's not a tool intended for the inexperienced at dealing with malware, e.g. in case its cleanup results in an unbootable PC. Malwarebytes seems to catch a bulk of the malware, including fake AVs that I've seen Symantec/Norton, McAfee, Avast, AVG, Microsoft, etc. all miss. Over the past year, I've only had seen one case where both Combofix and Malware bytes didn't clean a machine, but was able to find the culprit using the SilentRunners script (works similar to Hijackthis, but doesn't have removal capabilities.) Also, anti-malware tools typically work best when run in the safe mode, as some malware will only run in the normal mode.

I haven't used Spybot in a while, since I find it takes too long to run a scan, however, it's still very useful to have as it can be run from a bootable PE (e.g. BartPE), which is useful for cleaning a PC where the malware prevents tools from running in the safe mode or have another check for rootkits (which become well hidden when booting the main OS).