Antibiotic resistance: causes, consequences and means to limit it

GreenFacts
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Over the last century, antibiotics have radically changed the way we treat infections. They are an important tool for modern medicine, but unfortunately their misuse have led to the emergence of bacteria that are resistant to antibiotics. What has caused it and how can the spread of resistance be limited?

Antibiotic 
Resistance 
1 
This is a faithful synthesis and summary of 
several leading scientific reports. For the full list of 
sources, refer to the references section below. 
Antibiotic resistance: causes, consequences 
and means to limit it. 
Over 
the 
last 
century, 
antibiotics 
have 
radically 
changed 
the 
way 
we 
treat 
infections. 
They 
are 
an 
important 
tool 
for 
modern 
medicine, 
but 
unfortunately 
their 
misuse 
have 
led 
to 
the 
emergence 
of 
bacteria 
that 
are 
resistant 
to 
antibiotics. 
What 
has 
caused 
it 
and 
how 
can 
the 
spread 
of 
resistance 
be 
limited? 
What is the origin of resistance to antibiotics? 
The 
main 
origin 
of 
resistance 
to 
antibiotics 
is 
their 
misuse. 
As 
underlined 
by 
the 
European 
Centre 
for 
Disease 
Prevention 
and 
Control 
(ECDC) 
they 
are 
three 
main 
types 
of 
misuse: 
1. The 
unnecessary 
prescription 
of 
antibiotics 
for 
viral 
infections, 
against 
which 
they 
have 
no 
effect; 
2. The 
too 
frequent 
prescription 
of 
“broad-­‐ 
spectrum 
antibiotics”, 
in 
place 
of 
a 
better 
targeted 
antibiotic, 
through 
more 
precise 
diagnosis; 
3. The 
inadequate 
use 
by 
the 
patient, 
not 
respecting 
either 
dosage 
or 
duration 
of 
the 
treatment, 
which 
means 
that 
some 
of 
the 
bacteria 
may 
survive 
and 
become 
resistant. 
How does a bacteria become resistant to antibiotics? 
Some 
bacteria 
are 
naturally 
resistant 
to 
certain 
antibiotics, 
others 
can 
acquire 
resistance 
through 
mutations 
in 
some 
of 
their 
genes 
when 
they 
are 
exposed 
to 
an 
antibiotic. 
This 
resistance, 
natural 
or 
acquired, 
can 
spread 
to 
other 
bacterial 
species 
since 
bacteria 
can 
easily 
exchange 
genetic 
material 
from 
one 
to 
another, 
even 
if 
they 
are 
from 
different 
species. 
What are the possible consequences of antibiotic 
resistance? 
Many 
of 
the 
available 
treatment 
options 
for 
common 
bacterial 
infections 
are 
becoming 
more 
and 
more 
ineffective. 
As 
a 
consequence, 
there 
are 
situations 
where 
infected 
patients 
cannot 
be 
treated 
adequately 
by 
any 
of 
the 
available 
antibiotics. 
This 
resistance 
may 
delay 
and 
hinder 
treatment, 
resulting 
in 
complications 
or 
even 
death. 
Moreover, 
a 
patient 
may 
need 
more 
care, 
as 
well 
as 
the 
use 
of 
alternative 
and 
more 
expensive 
antibiotics, 
which 
may 
have 
more 
severe 
side 
effects, 
or 
may 
need 
more 
invasive 
treatments, 
such 
as 
intravenous 
injection, 
to 
be 
given 
in 
hospitals. 
A 
recent 
WHO 
report 
made 
a 
clear 
case 
that 
resistance 
of 
common 
bacteria 
to 
antibiotics 
has 
reached 
alarming 
levels 
in 
many 
parts 
of 
the 
world. 
In 
Europe, 
for 
example, 
there 
is 
an 
increase 
of 
the 
resistance 
to 
major 
antibiotics 
of 
common 
bacteria 
such 
as 
Escherichia 
coli 
which 
causes, 
among 
others, 
urinary 
tract 
infections, 
and 
also 
Staphylococcus 
aureus 
(the 
MRSA 
or 
methicillin-­‐resistant 
Staphylococcus 
aureus), 
Klebsiella 
pneumoniae, 
and 
Pseudomonas 
aeruginosa. 
For 
WHO, 
the 
consequence 
is 
that 
progress 
in 
modern 
medicine, 
which 
relies 
on 
the 
availability 
of 
effective 
antibacterial 
drugs, 
is 
now 
at 
risk. 
For 
instance: 
• Common 
infections 
such 
as 
pneumonia 
that 
can 
run 
in 
health 
care 
settings, 
may 
not 
respond 
to 
available 
or 
recommended 
drugs 
like 
penicillin, 
putting 
the 
lives 
of 
patients 
at 
risk; 
• Cystitis, 
one 
of 
the 
most 
common 
of 
all 
bacterial 
infections 
in 
women, 
may 
become 
untreatable 
or 
need 
to 
be 
treated 
by 
injected 
drugs, 
imposing 
also 
additional 
costs 
to 
the 
patients 
and 
to 
the 
health 
system 
in 
general; 
• Antibacterial 
drugs 
used 
to 
prevent 
infections 
after 
surgeries 
or 
to 
treat 
common 
infections 
in 
neonatal 
and 
intensive 
care 
may 
become 
less 
effective 
or 
ineffective. 
One 
issue 
stated 
in 
the 
WHO 
report 
is 
that 
there 
are 
very 
few 
antibiotics 
discovered 
and 
developed 
since 
1985 
to 
replace 
those 
becoming 
ineffective. 
Which are the main infections becoming resistant to 
antibiotics ? 
Bacteria 
causing 
a 
wide 
range 
of 
common 
infections 
may 
become 
resistant 
to 
one 
or 
many 
antibiotics: 
urinary 
tract 
infection, 
pneumonia, 
skin 
infection, 
diarrhea, 
bloodstream 
infection. 
The 
high 
proportions 
of 
resistance 
to 
third 
generation 
cephalosporins 
reported 
for 
E. 
coli 
and 
K. 
pneumonia, 
for 
example, 
means 
that 
treatment 
of 
severe 
infections 
caused 
by 
these 
bacteria 
must 
now 
rely 
mainly 
on 
another 
antibiotic 
family 
that 
is 
more 
expensive 
and 
may 
not 
be 
available 
in 
resource-­‐constrained 
settings. 
In 
addition, 
this 
can 
only 
last 
as 
long 
as 
these 
bacteria 
do 
not 
become 
resistant 
to 
this 
other 
alternative. 
Patients 
in 
hospitals 
are 
at 
special 
risk 
for 
infections 
by 
resistant 
and 
very 
pathogenic 
bacteria 
that 
can 
be 
present 
in 
hospitals 
and 
clinics, 
the 
so-­‐called 
nosocomial
infections, 
and 
which 
are 
unrelated 
to 
their 
reason 
for 
admission. 
What can be done to limit this increasing resistance 
to antibiotics? 
The 
first 
challenge 
is 
the 
significant 
gaps 
in 
surveillance 
of 
antibiotic 
resistance, 
says 
the 
WHO 
report. 
In 
2001, 
WHO 
and 
the 
Council 
of 
the 
European 
Union 
issued 
global 
strategies 
and 
guidelines 
to 
help 
countries 
setting 
up 
systems 
to 
monitor 
antibiotic 
resistance 
and 
to 
implement 
efficient 
actions, 
including 
public 
awareness 
campaigns. 
Nowadays, 
the 
most 
immediate 
and 
urgent 
concerns 
relate 
to 
antibiotic 
resistance 
in 
common 
bacteria. 
In 
line 
with 
the 
WHO, 
the 
ECDC 
(European 
Centre 
for 
Disease 
Prevention 
and 
Control) 
considers 
that 
three 
strategic 
areas 
of 
intervention 
should 
be 
prioritized 
and 
that 
each 
one 
can 
play 
an 
important 
role: 
1. Prudent 
use 
of 
available 
antibiotics 
and, 
when 
possible, 
infection 
prevention 
through 
appropriate 
vaccination; 
2. Hygienic 
precautions 
for 
the 
control 
of 
cross-­‐ 
transmission 
of 
resistant 
strains 
between 
persons, 
including 
screening 
for 
resistant 
strains 
and 
isolation 
of 
carrier 
patients; 
3. Research 
and 
development 
of 
antibiotics 
with 
a 
novel 
mechanism 
of 
action. 
Does the use of antibiotics in food-producing animals 
contribute to the problem? 
The 
major 
cause 
of 
antibiotic 
resistance 
in 
humans 
remains 
the 
use 
of 
antibiotics 
in 
human 
medicine, 
and 
the 
antibiotics 
used 
in 
food 
production 
contribute 
very 
little 
to 
the 
problem. 
However, 
since 
antibiotics 
used 
to 
treat 
and 
prevent 
bacterial 
infections 
in 
animals 
belong 
to 
the 
same 
chemical 
groups 
as 
those 
used 
for 
humans, 
animals 
may 
acquire 
bacteria 
that 
are 
resistant 
to 
antibiotics 
also 
used 
against 
human 
infections. 
Antibiotic 
Resistance 
2 
You 
can 
find 
this 
summary, 
along 
with 
a 
more 
detailed 
one 
on 
the 
GreenFacts 
website 
at: 
http://www.greenfacts.org/en/antimicrobial-­‐ 
resistance/index.htm 
The 
sources 
for 
this 
summary: 
• The 
initiatives 
of 
ECDC 
on 
antimicrobial 
resistance 
http://www.ecdc.europa.eu/en/healthtopics/anti 
microbial_resistance/pages/index.aspx 
http://www.ecdc.europa.eu/en/publications/Publ 
ications/antimicrobial-­‐resistance-­‐surveillance-­‐ 
europe-­‐2012.pdf 
including 
the 
“basic 
facts” 
: 
http://www.ecdc.europa.eu/en/healthtopics/anti 
microbial_resistance/basic_facts/Pages/basic_fac 
ts.aspx 
• Antimicrobial 
resistance 
-­‐ 
Global 
Report 
on 
Surveillance 
-­‐ 
WHO, 
2014 
http://www.who.int/drugresistance/documents/s 
urveillancereport/en/ 
• Global 
strategy 
for 
containment 
of 
antimicrobial 
resistance. 
World 
Health 
Organization, 
2001. 
http://www.who.int/drugresistance/WHO_Global 
_Strategy_English.pdf 
• The 
Antibiotic 
Resistance 
Threat 
in 
the 
United 
States 
2013 
– 
US 
Department 
for 
Health 
and 
Human 
Services 
-­‐ 
U.S. 
Centers 
for 
Disease 
Control 
and 
Prevention 
http://www.cdc.gov/drugresistance/threat-­‐ 
report-­‐2013/pdf/ar-­‐threats-­‐2013-­‐508.pdf 
Other 
references 
on 
the 
subject 
: 
-­‐ Origins 
and 
Evolution 
of 
Antibiotic 
Resistance 
J. 
Davies 
and 
D. 
Davies, 
Microbiology 
and 
Molecular 
Reviews, 
Vol. 
74, 
No. 
3 
p. 
417–433 
Sept. 
2010 
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2 
937522/pdf/0016-­‐10.pdf 
-­‐ The 
evolving 
threat 
of 
antimicrobial 
resistance 
-­‐ 
Options 
for 
action 
World 
Health 
Organization, 
2012 
http://whqlibdoc.who.int/publications/2012/9789 
241503181_eng.pdf?ua=1

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Antibiotic resistance: causes, consequences and means to limit it

  • 1. Antibiotic Resistance 1 This is a faithful synthesis and summary of several leading scientific reports. For the full list of sources, refer to the references section below. Antibiotic resistance: causes, consequences and means to limit it. Over the last century, antibiotics have radically changed the way we treat infections. They are an important tool for modern medicine, but unfortunately their misuse have led to the emergence of bacteria that are resistant to antibiotics. What has caused it and how can the spread of resistance be limited? What is the origin of resistance to antibiotics? The main origin of resistance to antibiotics is their misuse. As underlined by the European Centre for Disease Prevention and Control (ECDC) they are three main types of misuse: 1. The unnecessary prescription of antibiotics for viral infections, against which they have no effect; 2. The too frequent prescription of “broad-­‐ spectrum antibiotics”, in place of a better targeted antibiotic, through more precise diagnosis; 3. The inadequate use by the patient, not respecting either dosage or duration of the treatment, which means that some of the bacteria may survive and become resistant. How does a bacteria become resistant to antibiotics? Some bacteria are naturally resistant to certain antibiotics, others can acquire resistance through mutations in some of their genes when they are exposed to an antibiotic. This resistance, natural or acquired, can spread to other bacterial species since bacteria can easily exchange genetic material from one to another, even if they are from different species. What are the possible consequences of antibiotic resistance? Many of the available treatment options for common bacterial infections are becoming more and more ineffective. As a consequence, there are situations where infected patients cannot be treated adequately by any of the available antibiotics. This resistance may delay and hinder treatment, resulting in complications or even death. Moreover, a patient may need more care, as well as the use of alternative and more expensive antibiotics, which may have more severe side effects, or may need more invasive treatments, such as intravenous injection, to be given in hospitals. A recent WHO report made a clear case that resistance of common bacteria to antibiotics has reached alarming levels in many parts of the world. In Europe, for example, there is an increase of the resistance to major antibiotics of common bacteria such as Escherichia coli which causes, among others, urinary tract infections, and also Staphylococcus aureus (the MRSA or methicillin-­‐resistant Staphylococcus aureus), Klebsiella pneumoniae, and Pseudomonas aeruginosa. For WHO, the consequence is that progress in modern medicine, which relies on the availability of effective antibacterial drugs, is now at risk. For instance: • Common infections such as pneumonia that can run in health care settings, may not respond to available or recommended drugs like penicillin, putting the lives of patients at risk; • Cystitis, one of the most common of all bacterial infections in women, may become untreatable or need to be treated by injected drugs, imposing also additional costs to the patients and to the health system in general; • Antibacterial drugs used to prevent infections after surgeries or to treat common infections in neonatal and intensive care may become less effective or ineffective. One issue stated in the WHO report is that there are very few antibiotics discovered and developed since 1985 to replace those becoming ineffective. Which are the main infections becoming resistant to antibiotics ? Bacteria causing a wide range of common infections may become resistant to one or many antibiotics: urinary tract infection, pneumonia, skin infection, diarrhea, bloodstream infection. The high proportions of resistance to third generation cephalosporins reported for E. coli and K. pneumonia, for example, means that treatment of severe infections caused by these bacteria must now rely mainly on another antibiotic family that is more expensive and may not be available in resource-­‐constrained settings. In addition, this can only last as long as these bacteria do not become resistant to this other alternative. Patients in hospitals are at special risk for infections by resistant and very pathogenic bacteria that can be present in hospitals and clinics, the so-­‐called nosocomial
  • 2. infections, and which are unrelated to their reason for admission. What can be done to limit this increasing resistance to antibiotics? The first challenge is the significant gaps in surveillance of antibiotic resistance, says the WHO report. In 2001, WHO and the Council of the European Union issued global strategies and guidelines to help countries setting up systems to monitor antibiotic resistance and to implement efficient actions, including public awareness campaigns. Nowadays, the most immediate and urgent concerns relate to antibiotic resistance in common bacteria. In line with the WHO, the ECDC (European Centre for Disease Prevention and Control) considers that three strategic areas of intervention should be prioritized and that each one can play an important role: 1. Prudent use of available antibiotics and, when possible, infection prevention through appropriate vaccination; 2. Hygienic precautions for the control of cross-­‐ transmission of resistant strains between persons, including screening for resistant strains and isolation of carrier patients; 3. Research and development of antibiotics with a novel mechanism of action. Does the use of antibiotics in food-producing animals contribute to the problem? The major cause of antibiotic resistance in humans remains the use of antibiotics in human medicine, and the antibiotics used in food production contribute very little to the problem. However, since antibiotics used to treat and prevent bacterial infections in animals belong to the same chemical groups as those used for humans, animals may acquire bacteria that are resistant to antibiotics also used against human infections. Antibiotic Resistance 2 You can find this summary, along with a more detailed one on the GreenFacts website at: http://www.greenfacts.org/en/antimicrobial-­‐ resistance/index.htm The sources for this summary: • The initiatives of ECDC on antimicrobial resistance http://www.ecdc.europa.eu/en/healthtopics/anti microbial_resistance/pages/index.aspx http://www.ecdc.europa.eu/en/publications/Publ ications/antimicrobial-­‐resistance-­‐surveillance-­‐ europe-­‐2012.pdf including the “basic facts” : http://www.ecdc.europa.eu/en/healthtopics/anti microbial_resistance/basic_facts/Pages/basic_fac ts.aspx • Antimicrobial resistance -­‐ Global Report on Surveillance -­‐ WHO, 2014 http://www.who.int/drugresistance/documents/s urveillancereport/en/ • Global strategy for containment of antimicrobial resistance. World Health Organization, 2001. http://www.who.int/drugresistance/WHO_Global _Strategy_English.pdf • The Antibiotic Resistance Threat in the United States 2013 – US Department for Health and Human Services -­‐ U.S. Centers for Disease Control and Prevention http://www.cdc.gov/drugresistance/threat-­‐ report-­‐2013/pdf/ar-­‐threats-­‐2013-­‐508.pdf Other references on the subject : -­‐ Origins and Evolution of Antibiotic Resistance J. Davies and D. Davies, Microbiology and Molecular Reviews, Vol. 74, No. 3 p. 417–433 Sept. 2010 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2 937522/pdf/0016-­‐10.pdf -­‐ The evolving threat of antimicrobial resistance -­‐ Options for action World Health Organization, 2012 http://whqlibdoc.who.int/publications/2012/9789 241503181_eng.pdf?ua=1