Drug Double-Team Blocks Bacterial Resistance

Photo taken by Steve Mestdagh

As prosthetic implantation becomes routine, more is learned about streamlining the process and preventing accompanying complications. One major problem seen is prosthetic joint infection (PJI). A German research team recently found a way to decrease PJI caused by drug-resistant bacteria.

The drug of choice to fight most PJIs is rifampicin as it is very potent against gram positive bacteria, the most common offenders. Intravenous rifampicin blocks the creation of RNA and the resulting bacterial machinery needed to sustain its life. As this drug is widely used, resistant strains mutate into existence frequently. Hypotheses emerged stating that coupling administration with vancomycin, a drug that inhibits cell wall formation allowing bacteria to pop themselves, could prevent the seen resistance. To test the theory, titanium discs were placed into a solution containing between 2×103 and 2×106 colony forming units/well of Staph aureus bacteria and growth medium. This was followed by evaluation of colony growth post-incubation measured by fluorescence. Unlike the control group, blank titanium discs, discs were accompanied by either tethered vancomycin or tethered vancomycin and soluble rifampicin.

As expected, ample growth was found on the control discs. Vancomycin tethered discs showed inoculum dependant growth as five fold less than control for inocula of 2×103 (P=0.024), 2×104 (P=0.047), and 2×105 (P=0.022) CFU/disc. However, at 2×106 CFU/disc, fluorescence readings were similar to the control plate (1.5 fold ratio with P=0.1). This indicated a very small effect of vancomycin at high concentrations of bacteria. Following, Vancomycin discs were tested with soluable rifampicin added. Separately, 0.5 mg/L of vancomycin and 0.015 mg/L of rifampicin were needed to prevent growth of a 5×104 CFU inoculum. However together, 0.25 mg/L vancomycin and 0.008 mg/L rifampicin was sufficient to inhibit growth.

Finally, the combination of drugs was tested against a mutant strain of S. aureus that is resistant to rifampicin. The combination of drugs completely inhibited growth and disc adherence of the resistant strain resulting in a bacteria free disc.

These results prove extremely useful in preventing prosthetic join infection. Using smaller doses of drugs, researchers were able to inhibit bacterial growth and kill initially drug-resistance bacteria.

Further expansion of combination drug use may help prevent other resistant bacterial strains from being born. This could mean fewer drugs needing to be developed and lower costs of treatment.

Reference:
Martin Rottman, Joel Goldberg, S. Adam Hacking. 2012. Titanium-Tethered Vancomycin Prevents Resistance to Rifampicin in Staphylococcus aureus in vitro. PLoS ONE. http://dx.doi.org/10.1371/journal.pone.0052883

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