First--and most obvious--is the fact that the bacteria remain bacteria, that no essential change in the species has occurred. That is, that while the new resistance has a significant effect on the species likelihood to persist (survive), the change is nonetheless extremely slight with regard to the organism as a whole. Indeed, we now know that bacteria alive today are essentially indistinguishable from the first bacteria living on the planet. This is (to say the least) evidence contrary to the expectations of macroevolutionary theory.
Second, the latest technology from genetics, genomics, and pathology allows us to examine both the types of mutational changes involved in the acquisition of resistance and the facility and frequency of such mutational changes.
In his latest book, The Edge of Evolution, biochemist Michael J. Behe does just such an examination, and his conclusions are anything but supportive of neo-Darwinism. Behe looks at systems involving extremely large population sizes for which we can determine the frequency and type of beneficial random mutations: malaria cells, human blood cells (in their response to invading malarial cells), HIV, and E. coli.
As to the type of mutation occurring in these systems, the changes that represent a specific benefit (to the malarial cell in its efforts to parasitize humans or in the human blood cells in their efforts to defeat malaria) actually involve a breaking of an existing gene product. That is, a genetic change that confers an adaption in this very specific regard is an abandoning of a previous function. It is not the mutational advance spoken of so easily by Darwinists, but a degradation of existing function.
Moreover, the likelihood of such random mutations--as determined by its frequency in these systems--is extremely small (as Behe takes several chapters to carefully demonstrate). If you're interested in this stuff, by all means get Behe's book, but here's an example of the conclusions to which this research leads...
The likelihood that Homo sapiens achieved any single mutation of the kind required for malaria to become resistant to chloroquine--not the easiest mutation, to be sure, but still only a shift of two amino acids--the likelihood that such a mutation could arise just once in the entire course of the human lineage [given] ten million years, is miniscule... On average, for humans to achieve a mutation like this by chance, we would need to wait a hundred million times ten million years. Since that is many times the age of the universe, it's reasonable to conclude the following: No mutation that is of the same complexity as chloroquine resistance in malaria arose by Darwinian evolution in the line leading to humans in the past ten million years.Again, we see that the evidence appealed to most readily by modern Darwinists turns out, on closer inspection, to tend toward falsifying the theory for which they argue.
Instead of concentrating on us humans, we can look at the odds another way. There are about five thousand species of modern mammals. If each spoecies had an average of a million members, and if a new generation appeared each year, and if this went on for two hundred million years, the likelihood of a single [such mutation] appearing in the whole bunch over that entire time would be only about one in a hundred.