My approach is get rid of the numbers between the two characters '.' and '+' first by replacing those numbers to _.

import re

input_string = "manual__2025-04-08T11:37:13.757109+00:00"
result = re.sub(r'\.(\d+)\+', r'_', input_string)
result = result.replace(':', '_').replace('+', '_')

print(result)