I think you have to take the sample first and and culture in a media containing the the pharmaceuticals of choice. If there is any that forms colonies then you can isolate and pure culture the colony.

I'd do an enrichment of the surface water first before trying to culture it on a plate. If you try to culture directly onto a plate you may lose a significant portion of the organisms who just can't survive on the typical medium - that whole "Great Plate Count Anomaly" thing.

An enrichment should be relatively simple out of pond/lake water. A small sample of river water, plus maybe some DI water, supplemented with the pharmaceuticals of your choice and leave it out at room temperature or in an incubator for several days. Then you can do some FISH, or some 16S amplification on the sample to get clades of relatedness. Once you have clades/identities through the sequencing, you can probably more reliably find a way to culture it in vitro. Though there is always the chance that anything you find may not be culturable in the lab.

As Kenneth wrote, it's very rarely recommended to culture environmental samples directly to plates, since it can lead to a loss of microbial diversity. You could do cultures in both Nutrient Broth (both with and without the pharmaceutical) and M9 mineral medium (some with glucose added, others with 0.5-1% glucose and the pharmaceutical compound of choice, and finally M9 cultures with the pharmaceutical as the sole carbon source). I suggest adding glucose to the M9 Broth just in case of diauxic behavior. Be sure to use a sufficient amount of sample and to adjust the pH of the cultures to the pH of the original sample.

The cultures in NB and M9 without pharmaceutical compounds would give you a "greater view" of the microbiota in your sample and would allow you to potentially isolate m.o. that could degrade your compounds under different culture conditions (Temp, agitation, pH, different media, etc.). In any case, after growth in your broths then isolate on plates (basal and enriched media for both G(-) and G(+) m.o.) until you have completely axenic cultures... and yes, be prepared to make a lot of plates.

In my case when ever i wanted to isolate any microbes that can degrade or produce enzymes of interest, i'll do the primary screening. Primary screening was done by incoorperating the enzyme of interest into the minimal agar/broth. This will enable us to obtain the targeted microbes fast. At this stage, i personally felt that only the strong microbes will be able growth due to the media that we used are not selective towards one microbes but a minimal media containing the enzyme of interest as our main ingredient.

Well, I would go for enrichment of the sample water, followed by trying to grow the microbes in it on a plate containing a medium supplemented with the pharmaceutical compound of interest. The colonies that come up, if any, can then be isolated and grown separately under axenic conditions.

Thank you all for the great suggestions, if you have a protocol that I can try to follow it will be of great help. I have little experience in microbiology so a specific method will be awesome.

R3A agar is fairly effective for subculuturing, especially in making the transition from a low nutrient environment. R3A also helps with the recovery of isolates from R2A agar.