The document discusses the growing threat of antibiotic resistance and the possibility of entering a "post-antibiotic era" where antibiotics are no longer effective. It outlines how overuse and misuse of antibiotics has led to more drug-resistant bacteria. The consequences of a world without effective antibiotics would be severe, similar to times before antibiotics when many common infections were fatal. Solutions proposed include developing new antibiotics, using existing drugs in new ways, and improving antibiotic stewardship to slow the rise of resistance. The insurance industry may need to develop new products that address higher mortality risks and increased rates of chronic illnesses if antibiotic resistance continues to spread.

1. What if…we entered a post-antibiotic era?
A “what if” question is an extremely useful
question: it enables us to enter the realm of
possibilities, identify the most likely scenarios and
think through the potential consequences. Based
on this analysis, we can highlight the areas that
we need to look into now in order to better
prepare ourselves for the future.
One morning in January 2013, Brian Pool, an English
teacher, was on his way to work at a Vietnamese
school when he suddenly collapsed. On admission to
hospital he was diagnosed as having suffered from a
haemorrhagic stroke and following emergency
surgery was flown back home to Wellington, New
Zealand. However, despite successful surgery he
remained unwell, with evidence of a major infection
from which he died in an isolation unit some five
months later.
Subsequent tests showed that Brian was carrying a
strain of bacterium known as KPC-Oxa 48, a so called
superbug. As the hospital’s microbiologist later
stated "Nothing would touch it. Absolutely nothing.
It's the first one that we've ever seen that is resistant
to every single antibiotic known...”i
. The tragic story
of Brian Pool serves as a powerful illustration of what
happens when antibiotic resistance arises.
The rise of the super-bug
Rewind to the early 2000’s and a wave of bacteria
began to exhibit invulnerability to a group of drugs
known as carbapenems, medicines considered a last
line of defence against virulent bugs like E.coli,
Klebsiella (of which KPC-Oxa 48 is a mutant strain),
and Acinetobacter. However, there remained one last
weapon of resort, colistin. Despite being an
inexpensive drug it had largely fallen out of use due
to toxic side effects on the kidneys and nervous
system, amongst others. So colistin became that last
line of defense until, 2015 when Chinese scientists
reported the emergence of an E.Coli strain that had a
gene, MRC-1, that defeated even that.
As one scientist put it to the BBC:
“If MRC-1 becomes global, which is a
case of when not if, and the gene aligns
itself with other antibiotic resistance
genes, which is inevitable, then we will
have very likely reached the start of the
post-antibiotic era.”
Antimicrobial resistance – the coming
apocalypse!
Issue No. 72, November 2016
infocus

2. Hannover Re | 2
The Threat
A grave prediction, and a threat so serious that in
September 2016 the United Nations General
Assembly convened to discuss the problem, only the
fourth time a health issue has triggered such a
meeting in the UN’s history .
So what does a ‘post-antibiotic’ world look like, how
did we get here, what can be done and what would it
mean for the insurance industry if the worst is
realized?
Outside of war and famine, some of the biggest killers
in human history have included the bubonic plague,
cholera, syphilis, tuberculosis, scarlet fever and
pneumonia, all of which have bacterial causes. Even
deaths linked to influenza, a virus, are largely due to
the bacterial pneumonia it triggers. As a result it is no
exaggeration that alongside vaccination, the
discovery of antibiotics ranks as one of the greatest
scientific achievements ever made, by either
eradicating or making certain endemic microbial
diseases simply less lethal.
Graph 1: How the most common causes of death have changed in
the last century
For a glimpse of what a ‘post-antibiotic’ world looks
like we need only to view the way we lived and died
before Alexander Fleming created the compound that
would become penicillin in 1944.
At the beginning of the 20th
century 40% of all deaths
were as a result of infections ii
, 40 in 1000
pregnancies resulted in the mother’s deathiii
and 50%
of all deaths in children aged 5-9 were from
infectious diseases such as scarlet feveriv
. Today,
only 1% of all deaths are related to infections (see
graph 1v
), maternal deaths from pregnancy related
sepsis is 0.29 per 100,000vi
, and only 2.6% of deaths
in children aged 5-18 are from infectionsvii
. The
successful fight against infectious disease is one key
explanation of why demographically we have shifted
from a world troubled by acute deadly disease that
affected primarily the young, to one where chronic
illness of the elderly is becoming the main challenge.
Antibiotic Resistance
The very success of antibiotics is one of the reasons
behind the rise in microbial resistance that occurred
over the last few decades. People fall ill with a cough,
cold or any infection and visit their GP with the
expectation that they should get antibiotic treatment
even though, in vast majority of cases, the illness is a
self-limiting viral one. As a result, it is estimated that
up to ten million unnecessary prescriptions for

3. Hannover Re | 3
antibiotics are currently written each year in the UK
aloneviii
.
Table 1: Know your Germs - microbial disease:
Bacterium, virus, fungi and protozoan
Bacterium Single cell organisms that are the smallest and oldest
form of life on the planet. They exist in infinite
number but only 1% cause harm to humans.e.g.:
Yersinia pestis (plague), Streptococcus pneumoniae,
Escherichia coli.
Viruses Small infectious pathogens that can only exist within
living cells. Viruses require specific methods to be
spread, by disease bearing organisms called vectors
or by transmission though touch, or by coughing or
sneezing, As well as infectious disease viruses are
thought to play a role in triggering cancer and
inflammatory disease. Until recently form of
treatment is vaccination but in the wake of HIV anti-
viral drugs have been discovered. e.g.: Small pox,
Rubella (Measles), Influenza, HIV, Ebola, Varicella
Zoster (chickenpox), Rhinovirus (cold).
Protozoa One celled organisms that exhibit animal like
behaviour (movement and predation) e.g.:
Plasmodium (Malaria).
Fungi Plant like multi-celled organisms – that rely on other
organisms to get food.
e.g.: Candida Pneumocystis jirovecii(Pneumocystis
pneumonia)
For family doctors, distinguishing between such
relatively harmless viral diseases and a potentially
more serious bacterial one is almost impossible.
Consequently up to 90% of doctors stated that they
felt pressurised into prescribing anti-biotics, leading
to 97% of patients who ask for them, getting themix
.
In addition to over-prescription, people simply do not
complete the course of treatment, potentially leaving
some bacteria alive and a pool of bugs that have been
exposed to but not killed by the drugs. Worst still, is
the way people disposed of the unused drugs, with
over half flushing them down the toiletx
.
However, perhaps the biggest cause of antibiotic
resistance is their use in animal feed.
The way modern factory farming has developed
means animals are often kept in close unhygienic
proximity, an ideal breeding ground for bacterial
growth.
In order to keep losses of animals to a minimum
some farmers use or have used antibiotics
prophylactically, with the end result being that
produce from these animals (meat, eggs, milk etc.)
pass into the food chain. Indeed the colistin resistant
strain, MRC-1 discovered in China probably arose in
such circumstances.
Antibiotic Resistant Bacteria
Of course as bacteria are living organisms, they
procreate and pass on their genes to their
descendants. As with other organisms, through
natural selection and random mutation, certain traits
to assist with survival are passed on. These traits
could be ways to defeat antibiotics. Indeed Fleming
predicted as far back as 1945 that such things would
naturally occurxi
.
The combination of all the factors listed above has
meant that microbial resistance has accelerated to a
point where we are on the cusp of a potential health
crisis.

4. Hannover Re | 4
Table 2: How antibiotics work
The drugs work in two essential ways:
1. As ‘Bactericidal’, killing the bacteria by destroying or
effecting the synthesis of cell walls (e.g. : penicillin,
carbapenems, fluoroquinolones)
2. Or as ‘Bacteriostatic’, effecting reproduction of cells
preventing RNA/DNA replication or protein production
and allowing the body’s own defences time to kill off
the remaining bugs (e.g. erythromycin).
Antibiotics can also be described by the range of cells they affect;
by being narrow spectrum (i.e. only affecting specific types or
subtypes of bacteria) or broad spectrum which affect a variety of
types and families of bacteria.
Other ways of classification is by grouping them by molecular
structure, for example tetracyclines are so called because of their
four ring structure. Generally speaking antibiotics of similar
chemical structure behave in the same way and have similar side
effects.
In the face of such a potential crisis, many
governments have created specialist organisations to
co-ordinate the fight against microbial resistance at
both a national and international level. The UK
Government, for example, created a Review on
Antimicrobial Resistance which has stated that the
cost of inaction could mean an estimated worldwide
healthcare bill of £69 trillion a year and cause an
increase in annual deaths from untreatable infections
from the current 700,000 a year to a staggering 10
million by 2050xii
. Indeed the UK’s Chief Medical
Officer, Professor Dame Sally Davies, has stated that
antimicrobial resistance is “a ticking time bomb” as
grave as other potential threats such as terrorism,
pandemic flu and major floodingxiii
.
Indeed the risk from lack of protection from bacteria
will affect many aspects of life we currently take for
granted. Surgery, even minor, will be a potentially
life threatening vector for infectious disease taking
hold. And as for more invasive, innovative techniques
such as organ transplantation - what would be the
point if over half of patients succumb to post-
operative sepsis?
Numerous other things could put people in jeopardy;
anything requiring open access to the body
(catheterisation or dialysis), implantation of devices
such hips or knees or defibrillators, how we treat
people after even minor accidents and even getting a
tattoo could all become life-threatening situations.
A difficult simple solution
The simplest solution is of course the obvious one, to
discover and manufacture new antibiotics, but this is
much more difficult and more complex in practice.
Discovering a new antibiotic usually involves taking
samples from a variety of sources and looking for
compounds that have antibacterial properties. The
process is, however, a long and laborious one with
perhaps one in a million samples yielding any
potential. Any such compound would then need to be
synthesised and go first through laboratory and
animal testing before finally entering human trials.
Such an exercise has been estimated to take around
15 years and cost in the region of £100 million, so
little wonder perhaps that no new antibiotics have
been patented for thirty years xiv
. The commercial
reality has also been that with seemingly very
effective, cheap antibiotics readily available to treat
acute infections over this period, the pharmaceutical
industry has focused almost entirely on serving the
bigger, more profitable demand for treatments of
chronic illness in an ever aging society. This may
change following a joint declaration on the issue
between ‘Big Pharma’ and governments at the World
Economic Forum in Davos in January 2016xv
.
Medicine strikes back
And yet there is hope. This year alone has seen a
number of exciting new discoveries, often from
unexpected areas. Bioprospecting of the nests of
leaf-cutter ants has shown promise as these insects
secrete both anti-bacterial and anti-fungal agents to
protect their homesxvi
. A little closer is the compound
lugdunin, which has been retrieved from a bacterium
which lives in the human nose; this has been shown
to act against Staphylococcus aureus, one strain of
which is the superbug MRSAxvii
.
Finally and perhaps most intriguingly, is the work of
an Australian PhD student, who has developed a
polymer using nanotechnology called SNAPPS
(Structurally Nano-engineered Antimicrobial Peptide

5. Hannover Re | 5
Polymers) that can effectively destroy bacterial
cellsxviii
.
Nanotechnology
Whilst promising, much of this research is potentially
decades away from clinical use in every day settings.
As a stop gap additional treatments are being
proposed which involve using existing antibiotics in
conjunction with other drugs to boost them into
antibiotic resistance breakers (ARBS). The charity,
Antibiotic Research, for example, proposes to focus
efforts on three of the more endemic gram negative
bacteria which cause 50% of all hospital infections
(Klebsiella pneuomoniae, Escherichia coli and
Acinetobacter baumanii). In addition a new blood test
has been developed to allow family physicians to
distinguish between viral and bacterial infections
when a patient presents at their surgery; this should
cut down on unnecessary prescriptions of
antibioticsxix
. This strategy of both long and short
term solutions should prevent some of the worst
ravages of this rise in antibiotic resistance.
The impact on Protection
Whatever the outcome of this race, there remains a
potentially huge impact on the life insurance sector,
given the number of lives potentially affected.
Generally, the industry bases its underlying pricing
assumptions on improving trends in mortality and a
gradual shifting of incidence in morbidity to older
ages. In a post antibiotic world death rates would
rise significantly, perhaps effecting younger cohorts
disproportionately. As more people die in early or
middle adulthood fewer people will survive to old age.
A corresponding fall in incidence rates of certain
chronic diseases could make CI less relevant and see
the demand for longevity products fall. We usually
associate the term pandemic with viral diseases
which emerge in a frighteningly rapid way (such as
‘Swine flu’ or HIV). However a strain of highly
infective bacterial disease, such as scarlet fever,
resistant to current medication would be exactly that
and have just as dramatic an impact both societally
and economically.
What would a post-antibiotic world look like?
Such an apocalyptic scenario is unlikely. What is
more probable is the re-emergence of post-infective
complications; rheumatic valvular disease, persistent
urinary tract infections leading to renal failure,
deafness, blindness and early-onset chronic lung
disease, etc. It seems therefore, that the products the
life and health insurance industry could develop for
such a scenario would be even more important,
particularly those with disease paying triggers.

6. www.hannover-re.com
Indeed, exploring the addition of a ‘chronic post-
bacterial infection’ partial payment benefit under a
critical illness plan or one if the insured is infected
with a super-bug is one area of development. Other
ideas could include boosting payment for pregnancy
related complications involving pre or post-partum
infections.
Whilst the world is unlikely to see an apocalyptic
doomsday, society and the insurance industry still
needs to be prepared for a potentially difficult few
decades. At the very least we need to continue to
monitor claims trends and amend or evolve our
products and pricing as appropriate.
Paul Edwards
Manager, Medical Risk Research
Tel. +44 20 3206 1736
paul.edwards@hannover-re.com
Bibliography
i
New Zealand Daily Herald, Tuesday Nov 19
th
2013 Kiwi contracts
superbug resistant to every antibiotic
ii
Chamberlain, G., ‘British maternal mortality in the 19
th
and early
20
th
century’ JRSM, 2006 Nov; 99(11): 559–563
iii
Joe Hicks & Grahame Allen ‘ A Century of Change’ House of
Commons Library, Research Paper 99/111
iv
Ibid
v
GB Historical GIS / University of Portsmouth, England and Wales
through time | Life & Death Statistics | Cause of Death, A
Vision of Britain through Time
vi
Saving Lives Improving Mothers’ Care - Surveillance of maternal
deaths in the UK 2011-13 and lessons learned to inform maternity
care from the UK and Ireland Confidential Enquiries into Maternal
Deaths and Morbidity 2009-13; MBRRACE-UK, Dec 2015
vii
GB Historical GIS / University of Portsmouth, England and Wales
through time | Life & Death Statistics | Cause of Death, A
Vision of Britain through Time
viii
NICE Guidelines on Antibiotic Prescriptions, August 2015
ix
NICE https://www.nice.org.uk/news/article/calls-for-nhs-to-curb-
inappropriate-antibiotic-prescribing
x
Rosenblatt-Farrell, N. ‘The landscape of antibiotic resistance’
Environ Health Perspect. 2009 Jun; 117(6): A244–A250.
xi
Ibid.
xii
Review on Antimicrobial Resistance https://amr-
review.org/background
xiii
Professor Dame Sally Davies, to the BBC 11 March 2013.
http://www.bbc.com/news/health-21737844
xiv
The Daily Telegraph, 7
th
January 2016,
http://www.telegraph.co.uk/science/2016/03/14/first-new-
antibiotic-in-30-years-discovered-in-major-breakthroug/
xv
The Davos Declaration, Review on Antimicrobial Resistance
xvi
https://www.uea.ac.uk/leafcutter-ants
xvii
Science Magazine, Jul. 27, 2016,
http://www.sciencemag.org/news/2016/07/new-antibiotic-found-
human-nose
xviii
Shu J. Lam & Neil M. O'Brien-Simpson et al ‘Combating
multidrug-resistant Gram-negative bacteria with structurally
nanoengineered antimicrobial peptide polymers’ Nature
Microbiology,1 August 2016
xix
Medical Daily Jan.20 2016. http://www.medicaldaily.com/new-
blood-test-can-distinguish-between-viral-and-bacterial-infections-
may-curb-370226
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