NOVEMBER 2018 RESEARCH UPDATE

Love for Cipro

I love Cipro.  It is my antibiotic of choice when on the road to exotic destinations, where potable water only comes in bottles and where you have to check the seal on those to be sure.

I am not the only one who loves this drug.  Ciprofloxacin falls into the broader class of antibiotics referred to as second generation quinolones.  In 2010 (Wikipedia here),  over 20 million prescriptions were written for Cipro, making it the 5th most common antibacterial in the US.  People have appreciated Cipro since it was first introduced in 1987.  A single dose of Cipro for an adult is 250 mg.  A typical biosolids concentration is about 3 mg kg-1.  If you have concerns about pharmaceuticals in biosolids and antibiotic resistance, Cipro is a good place to start.  As cold and flu season is upon us, and as there are a new series of publications out on Cipro in biosolids from a very reliable source, that is what the November library is going to focus on.

We start with a paper by Caitlin Youngquist, a former local who had the privilege of working some with Craig and Andy at WSU for her MS.  This paper is with other cooperators and describes the fate of Cipro in the La Connor, WA, biosolids composting facility.  Concentrations of Cipro were tested, along with a range of other antibiotics, in the compost pile, prior to and post composting.  Concentrations of all measured compounds were lower in the final product than in the initial pile.  The authors also spiked some feedstock and put it back in the pile in small bags that could be retrieved.  They periodically took samples from the bags and shook them up with water and then tested the water for microbial toxicity.  A huge concern about antibiotics in soils is that they will harm the microbial community in soils.  Short answer: they didn’t.  So, Cipro and the other stuff tested goes away with composting, and microbes in the soil don’t flee the neighborhood when they hear that a ppb of Cipro has come to town. 

The next 4 papers are hot off the press (actually, to be published in 2019) and are from Harman Sidhu’s PhD thesis.  Harman had the privilege of working with George O’Connor at the University of Florida as his main advisor.  The work here on Cipro (and azithromycin) follows the same pattern as the work of two of George’s previous students, Liz Snyder and Manmeet Pannu (now with the WA DOE Biosolids program).  Both of those students did enough testing on the behavior of antimicrobials (TCC and TCS) to conduct risk assessments.  Both (except for one type of bird and TCC, if I remember correctly, posed negligible risks).  That is the conclusion here as well (spoiler alert).  But let’s walk through the papers to get there. 

The first paper (2nd in the library) tests the impact of both antibiotics added in ‘environmentally relevant’ concentrations in biosolids to earthworms and soil microbes.  That is a critical piece here -- the biosolids matrix can impact availability of these compounds and their behavior in soils.  Using relevant concentrations here is also very important.  Other studies have seen an impact when compounds are added to soil at unreasonable rates (rates not found in biosolids), and those results have been interpreted to have real world applications.  Not the case with these studies. Here biosolids were from the Chicago program and had relatively low concentrations of both antibiotics (1 ppm for Cipro and 0.6 ppm for Azithromycin).  Biosolids were added to soil at 20 Mg/ha, and in a second part of the study pure biosolids were spiked with the two compounds at low, medium and high concentrations.  The high concentration here was the 95th percentile concentration as reported in the 2009 EPA survey.  Harman tested earthworm survivability and accumulation for earthworms and nutrient cycling and respiration for microbes.  They also measured extractability and total concentrations of both antibiotics over time.  Again, apparently the antibiotics make good neighbors; they are quiet and spend most of their time at home.  In the soils and biosolids tested, in the presence of both antibiotics, the earthworms went about their business and the microbes theirs with no impact.  The earthworms did eat some of the antibiotics and had bioaccumulation factors greater than 1.  That means that the concentration in the worms was higher than in the soil.  This was the only concern of the work.  Finally, both antibiotics did not degrade quickly but had very low availability.  That low availability is likely at least partially responsible for the absence of harm in both studies so far.

The third paper in the library, and the 2nd from Harman, tested the potential for plant uptake and toxicity of the same two antibiotics.  Radishes, lettuce (both typically high accumulating crops) and tall fescue were grown in biosolids-amended soils.  Here they also included soils spiked with the antibiotics with no biosolids, admitting that they were just looking for trouble.  They didn’t find any.  Eat all of the lettuce and radishes you want- they may make you healthy, but they won’t expose you to antibiotics.  Cows, too, can eat all the tall fescue they want without fear of exposure to antibiotics.  Feedlots are where they have to worry about that. 

The 4th paper is the risk assessment.  In this paper, the researchers took all of the data that they had accumulated and used it to carry out a traditional risk assessment.  Both EPA methodology and World Health Organization methodology were used.  They considered potential impacts on people, soil microbes and predators.  Predators here refers primarily to animals like birds that eat bugs from soil.  Negligible risk was the conclusion.  You would have to have concentrations of antibiotics higher than are found in biosolids to even start to worry.

This all leads to the fifth and final paper in the library.  This could also have been the first paper in the library.  Here Harman looks at what happens when you add biosolids to soils that contain these two antibiotics.  They tested how strongly biosolids bind these two antibiotics as well as how strongly the antibiotics are bound in regular soils.  A range of methods were used to try to pry the antibiotics off the soil and biosolids.  It turns out that there was a great deal of hysteresis – meaning that sticking antibiotics onto biosolids was a whole lot easier than prying them off, with less than 3% of the total antibiotics coming off adsorption sites.  The conclusion from all of this is that the biosolids bind the antibiotics so tightly that they are pretty much a non-issue in a soil environment.

Hard to ask for better results than this.  Cipro is a great companion for travel and a great neighbor in a soil system.  I still love Cipro.