Unabsorbed Antibiotics and the Potential Contribution to Antibiotic Resistance
Yingying Hong and Paul Ebner - Purdue Animal Sciences
Antibiotics are used in animal agriculture to prevent or treat bacterial
infections. As with many medicines, antibiotics are not completely
absorbed by the animals. Inevitably, unabsorbed antibiotics, some in
their active forms, are excreted in animal waste. In the US, livestock
manure is generally applied to land as a fertilizer. While animals may
excrete unabsorbed antibiotics, much of the active form of the antibiotics
is destroyed during decomposition as the manure is stored prior to
application. (See link for further reading.) Once applied to land, antibiotics
further break down in the soil or through exposure to direct sunlight.
Thus, with each step, the concentration of antibiotics is significantly
reduced. However, in some cases, antibiotic compounds or residues
have been detected in surface waters surrounding livestock operations,
similar to what occurs with treatment of human waste water. The impact
of antibiotics in low concentrations in these specific locations remains
Much of the concern, however, revolves around the possibility that
unabsorbed antibiotics could lead to increases in antibiotic resistance
once the manure is applied to soil or through runoff from field where
manure was applied. Increases in antibiotic resistant bacteria result from
direct exposure of a bacteria community to an antibiotic. In this process,
the growth of antibiotic susceptible bacteria is inhibited due to the lethal
effect of the antibiotic, while the growth of antibiotic resistant bacteria,
even at low population, is not affected. With much less competition,
antibiotic resistant bacteria can then become a higher percentage of
the total bacterial population. While most of these antibiotic resistant
bacteria may indeed be harmless, some bacteria have the capacity to
transfer genetic traits (such as antibiotic resistance) horizontally to other
unrelated types of bacteria.
As with most drugs, an antibiotic needs to reach
a certain concentration to elicit a lethal effect
on a susceptible bacterium. The concentrations
of antibiotics in soil or water containing manure
are usually several hundred or thousand times
lower than such required concentrations. As such,
these concentrations were considered unable to
inhibit the growth of susceptible bacteria or select
for antibiotic resistance(Drlica 2003; Drlica and
Zhao 2007). However, the results of several recent
studies indicated that antibiotics at extreme low
concentrations should also be of concern. One such
study (Gullberg 2011) showed that, under laboratory
conditions, tetracycline and ciprofloxacin at very low
concentrations could increase the percentages of
resistant bacteria when both antibiotic susceptible
bacteria and resistant bacteria were present
together. This was done under laboratory conditions.
Thus, the question becomes whether antibiotic
selective effects can also be observed at such low
concentrations under environmental conditions.
Currently, research addressing this question is
largely lacking. One study exists which used
conditions resembling the field and traced the fate
of the antibiotic sulfadiazine throughout its journey
from oral administration in piglets to manure
storage to soil application(Heuer 2008). In this study,
the selection of antibiotic resistant bacteria was not
observed with the presence of sulfadiazine, or its
metabolites, at the final concentrations detected in
the soil. Unlike laboratory conditions, soil contains
very diverse bacterial populations. Coupled with
antibiotic adsorption to the soil matrix, and biotic/
abiotic degradation of antibiotics, emergence of
antibiotic resistant bacteria in soil is likely much
more difficult than in the laboratory (Chait 2012).
However, before we can better assess the risk of
environmental antibiotic residues, farms employing
practices that reduce the need for antibiotics should
be encouraged to continue doing so.
As with almost all issues we highlight on this series,
it is worth noting that land application of manure
containing unabsorbed antibiotics is not an issue
specific to CFOs. The use of antibiotics is a common
practice in conventional livestock and poultry
production—both large and small—to prevent or
treat animal diseases. CFOs, while holding more
animals by definition, however, could be predicted
to generate larger volumes of antibiotic-containing
Chait R, Vetsigian K, Kishony R. 2012. What counters antibiotic resistance in nature? Nature Chemical Biology. 8:2-5.
Drlica K. 2003. The mutant selection window and antimicrobial resistance. J Antimicrob Chemoth. 52:11–17.
Drlica K, Zhao XL. 2007. Mutant selection window hypothesis updated. Clin Infect Dis. 44:681–688.
Gullberg E, Cao S, Berg OG, Ilbäck C, Sandegren L, Hughes D, Andersson DI. 2011. Selection of resistant bacteria at very low antibiotic concentrations. PLoS Pathog. 7:e1002158.
Heuer H, Focks A, Lamshöft M, Smalla K, Matthies M, Spiteller M. 2008. Fate of sulfadiazine administered to pigs and its quantitative effect on the dynamics of bacterial resistance genes in manure and manured soil. Soil Biol. Biochem. 40, 1892–1900.