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danmap 2015 12 danmap - 20 years 2. has been monitored in e.
coli
both as commensals sampled from poultry, pigs and cattle, and meat products from these animals (so-called indicator strains), as well as pathogens from diagnostic samples from production animals ( diagnostic animal strains) and from blood and urine from infected humans ( diagnostic human strains). furthermore, within the frame of the danmap programme e.
coli
has been followed as com- mensal in gut flora from various cohorts of healthy humans (military recruits, nurses, random healthy volunteers etc.) and from environmental samples from wastewater and sludge. (see chapter 8.1. for more information on the e.
coli
from clini- cal submissions and textbox 7.2 for sampling from healthy humans during the years). collections of preserved e.
coli
isolates from all of the above origins have since been used in numerous research projects. various aspects of the bacterium have been studied: viru- lence genes,
antimicrobial
resistance
genes,
resistance
fit- ness-cost, e.
coli
clonal types and their possible spread from animals directly or via food to humans, in most cases taking into account
antimicrobial
use in animals and in humans. as one example, for the purpose of determining the role of animal derived e.
coli
strains in urinary tract infections in hu- mans, a large danmap collection of e.
coli
strains from cattle, pigs, poultry and meat products from these animals was used and compared to a collection of e.
coli
isolates from healthy humans and human urinary tract infections. comparison of virulence genes, phylotypes, pulse-field gel electrophoresis and
antimicrobial
susceptibility demonstrated complete over- lap between animal or meat and humans for some isolates and, in general,
antimicrobial
resistance
markers correspond- ed among all groups, which lead to the conclusion that e.
coli
uti in humans can be a zoonosis [jakobsen et al, 2012].
antimicrobial
resistance
monitoring - caveats with respect to using monitoring of
antimicrobial
resistance
levels in e.
coli
as a basis for understanding the relationship to
antimicrobial
consumption, for use in policies, intervention pur- poses or for treatment guidelines, respectively, it is extremely important to take into account the origin of isolates, i.e. the sampling strategy. in animals and food,
antimicrobial
resistance
in e.
coli
has been evaluated in isolates from samples obtained using randomized sampling strategies ? collecting samples from healthy animals at slaughter or fresh meat at wholesale and retail outlets. in contrast, the treating veterinarian or physician mostly obtains clinical samples of e.
coli
from infected animals or humans. this results in a tendency towards a skewed prevalence of antimi- crobial
resistance
, since gps may tend to submit samples from problematic patients only and not from those who respond to first-hand empiric
antimicrobial
treatment. this was shown in a study, where general practitioners were asked to submit all e.
coli
samples from patients with urinary tract infections irrespective of whether these were uncomplicated or compli- cated, i.e. recurrent infections or infections not responding to first-line
antimicrobial
s [kerrn et al, 2002]. the study demonstrated that e.
coli
from the urine of patients with uncomplicated urinary tract infections showed
resistance
levels about 50% lower than isolates from complicated cases e.g.
resistance
towards ampicillin 20% versus 40%, sulfon- amide 20% versus 40%, and trimethoprim 10% versus 20%, respectively [kerrn et al]. the higher
resistance
levels cor- respond to those levels usually reported in danmap reports in e.
coli
from urinary tract infections from primary care and hospitals as well as from bacteraemia cases (see all danmap reports from 1996 ? 2015, chapter 8 on clinical
resistance
in humans). several investigations from danish clinical microbiol- ogy laboratories also showed, that the first e.
coli
isolate from a patient usually is more susceptible than later isolates from the same patient (thøger gorm jensen, henrik schønheyder, jens kjølseth møller, personal communication). all the above adds a cautionary note for the use of
antimicrobial
resistance
monitoring data for research and policy purposes. relationship between
antimicrobial
use and
resistance
even so, danmap has amply demonstrated a relationship between
antimicrobial
use and
antimicrobial
resistance
levels with e.
coli
as the indicator bacterium both in production animals and in humans. figure 1 illustrates in rough terms the relationship between
antimicrobial
consumption by species and the
resistance
levels in e.
coli
from poultry, cattle and pigs when taking into account the size of the biomass treated. diagnostic samples show the highest
resistance
levels. among indicator e.
coli
,
resistance
levels are clearly highest in pigs, which have the highest
antimicrobial
use both for treatment and meta-prophylaxis. an example from humans is illustrated in figure 2, which shows ciprofloxacin use in primary health care and ciprofloxa- cin
resistance
in e.
coli
from urine samples in primary care. both sets of data are from 2000 - 2015 (modified from this year?s report). there is a clear correlation association between the increase in use and concomitant increase in
resistance
from 2000 - 2009, after which a levelling off in the
resistance
level reflects a levelling off in the consumption from 2009 and onwards. one of the reasons for the rapid increase in cipro- floxacin use during the `00´s was a significant reduction in price of ciprofloxacin after the market was opened to generic ciprofloxacin in 2002 (danmap report 2003). these examples of a relationship between
antimicrobial
use and
resistance
led to policy changes both in the veterinarian and the human field, e.g. a general warning against wide- spread use of ciprofloxacin in primary care in denmark was issued by the danish health authority (sundhedsstyrelsen) in 2012.
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