Mike the Mad Biologist

You might find it hard to believe, but determining whether restricting antibiotic use leads to decreased resistance is actually not very straightforward. That’s because antibiotic resistance genes can be linked to–that is, they travel along with–other resistance genes or even genes that are favored for some other reason. So even when an antibiotic is no longer used, the use of other antibiotics (or other antibacterials such as quarternary ammonium compounds or colloidal silver) can keep these genes around.

But quinolone antibiotics such as ciprofloxacin (“Cipro”), which are used to treat many different diseases including urinary tract infections, are different.

In most cases, resistance to quinolones is due to a point mutation in the bacterial chromosome, the smallest possible scale of change in DNA. These mutations are usually very harmful to the bacterium: in the case of ciprofloxacin, the genes involved in DNA replication are much, much less efficient, dramatically inhibiting bacterial cell division. That seems to be why a recent Israeli study reports that reduction in ciprofloxacin use (the Israeli government wanted to maintain its effectiveness against a potential bioterror attack) led to a decrease in quinolone resistant E. coli associated with urinary tract infections:

We found a significant decline in quinolone consumption, measured as defined daily doses (DDDs) per month, between the preintervention and intervention periods (point estimate, −1827.3 DDDs per month; 95% confidence interval [CI], −2248.8 to −1405.9 DDDs per month; p < 0.001 ). This decline resulted in a significant decrease in E. coli nonsusceptibility to quinolones, from a mean of 12% in the preintervention period to a mean of 9% in the intervention period (odds ratio, 1.35; p = 0.014). The improved susceptibility pattern reversed immediately when quinolone consumption rose. Moreover, a highly significant inverse relationship was found between the level of quinolone use (regardless of intervention period) and the susceptibility of E. coli urine isolates to quinolone (odds ratio, 1.70; 95% CI, 1.26-2.28). During the months of highest quinolone use (8321 DDDs per month), the proportion of nonsusceptibility was 14%, whereas during the months of lowest quinolone use (4027 DDDs per month), the proportion of nonsusceptibility was 9%. An average decrease in resistance of 1.16% was observed for each decrease of 1000 DDDs.

Basically, a fifty percent reduction in quinolone use led to a ~33 percent reduction in quinolone resistance. What’s interesting is that when use rose, quinolone resistance rose, and when use dropped, resistance dropped–and did so very rapidly–within a month or two.

This is some welcome news.

Cited article: Gottesman, B.S., Carmeli, Y., Shitrit, P., and Chowers, M. 2009. Impact of quinolone restriction on resistance patterns of Escherichia coli isolated from urine by culture in a community setting. Clinical Infectious Diseases 49:869-875. DOI: 10.1086/605530

Comments

  1. #1 NewEnglandBob
    August 26, 2009

    Yes, good news, but just a win in one skirmish of the war.

  2. #2 Staphylococcus
    August 26, 2009

    “These [point] mutations are usually very harmful to the bacterium”

    Incorrect. Most do nothing whatsoever either way. You are correct in saying that this particular mutation (in the gene for DNA gyrase IIRC) is harmful (for a given definition of harmful, since it isn’t lethal and merely slows the process down) except when under selective pressure to maintain it.

  3. #3 JohnV
    August 27, 2009

    @2:

    He specifically indicated that the point mutations in question are the ones that provide some level of quinolone resistance, not all possible point mutations in the organism.

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