stroy bacteria in a similar fashion. The World Health Organization considers both
penicillins and tetracyclines to be Critically Important in human medicine, unlike the
FDA, which considers them only Highly Important. Another drug class, fluoroquinolones, considered Critically Important by FDA, was successfully banned for extralabel use in food animals and any use was banned in poultry over concerns of
Antibiotic resistance impacts public health when people consume food contaminated with antimicrobial-resistant bacteria resulting from the exposure of food animals
to antimicrobials, including cephalosporins. Gram-negative bacteria acquire or have
innate resistance to cephalosporin through b-lactamases, which inactivate the drug itself.
8 CMY- 2, a type of AmpC enzyme, and the extended-spectrum b-lactamases
(ESBLs) are found on the chromosomes of
most Enterobacteriaceae and on plasmids in
Salmonella, Escherichia coli and other
Enterobacteriaceae. CMY- 2 and ESBLs provide
resistance to first-, second- and third-generation cephalosporins. CMY- 2 is the b
-lac-tamase most associated with Salmonella
from isolates that display resistance to ceftiofur and increasing resistance to ceftriaxone.
9–11 ESBLs present in bacteria of
human concern include CTX-M, which is
plasmid-mediated and has the potential to
provide resistance to all cephalosporins.
Although now dominant only in European
countries, CTX-M enzymes are gaining a
foothold in the United States but do not
12, 13 When mobilized,
CTX-M enzymes often can be found on
large multidrug-resistant plasmids. FDA is
concerned that cephalosporin resistance
may escalate as CTX-M becomes more
widespread. Severe bacterial infections resistant to cephalosporins, without FDA’s continued action, may face treatment failures from ineffective antibacterial regimens, increasing the likelihood of death.
Of particular concern is the evidence of cross-resistance among drugs in the broad
cephalosporin class and the increase in reports of CMY- 2 and CTX-M b-lactamases,
which transfer cephalosporin resistance between enteric bacteria.
9 The surveillance efforts of both the NARMS as well as the Canadian Integrated Program for Antimicrobial Resistance Surveillance have noted both in animal and human isolates the
acquired resistance to b-lactams. Resistance to ceftiofur corresponds with resistance to
ceftriaxone, conferred by CMY- 2, and provides resistance to first-, second- and third-generation cephalosporins. Resistance to ceftiofur compromises the efficacy of ceftriaxone, a first-line therapy for treating human salmonellosis. CMY- 2, in addition to
providing ceftiofur and ceftriaxone resistance, conveys resistance to many other b
-lactams, including ampicillin and amoxicillin.
14 The concern over the pervasiveness and
range of CMY- 2 in the ceftiofur and ceftriaxone surveillance data helps provide the
basis for FDA’s action as it supports the findings that cephalosporin use in food animals is contributing to an upsurge in cephalosporin-resistant pathogens.
The recent issuance is not an all-out prohibition of cephalosporin use in food animals. Many have complained that it is watered down compared with what was put
forth in 2008, while some former critics now indicate that it is more reasonable.
“...FDA has consistently
believed, for several
decades now, that there
are human health risks in
doses of medically
important antibiotics in
Prohibition in the 21st Century
As stated in the prohibition issuance, and in many agency documents in regard to
the use of antimicrobial drugs in animals, “When considering the foodborne pathway,
the potential for human exposure to an-
timicrobial-resistant pathogens is signifi-
cantly less for food derived from minor
species than it is for food derived from
the food-producing major species. The
exposure potential is less in part because
the amount of food derived from cattle,
swine and poultry is much greater than
the amount of food derived from sheep,
goats and aquaculture, the minor species
from which the most food is derived.”
Minor species are defined as animals
other than cattle, swine, chickens,
turkeys, horses, dogs, cats and humans.
At this time, FDA is not planning to
prohibit extralabel use of cephalosporins
in food-producing minor species because
they do not believe that this use repre-
sents a significant risk to the public
health, since these species are consumed
16 Also, because
cephalosporins are approved for use in
sheep and goats, there is less potential
for extralabel use in these species, ac-
cording to the agency. Although people
may consume these animal species less
often, any practice that selects for resist-
ance genes is concerning.