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BACKGROUND

Bacterial resistance to antibiotics: a major issue in terms of public healthcare

Due to its global spread and its speed of development, antibiotic resistanceAntibiotic resistance
Infections caused by antibiotic-resistant bacteria are increasing steadily worldwide in hospitals as well as in the community. These infections often have more severe outcomes than those caused by so called "sensitive" bacteria. As a consequence, they also require more expensive second-line treatments as well as a more careful and costly follow-up care for patients.
is currently one of the most worrying Public Health trends.

Since no new class of antibiotics is expected for the coming years, antibiotic resistanceAntibiotic resistance
Infections caused by antibiotic-resistant bacteria are increasing steadily worldwide in hospitals as well as in the community. These infections often have more severe outcomes than those caused by so called "sensitive" bacteria. As a consequence, they also require more expensive second-line treatments as well as a more careful and costly follow-up care for patients.
threatens the effectiveness of many drugs used today,



putting at risk or even reversing the significant progresses made so far in the fight against infectious agents (1).

A recent report released by the ECDC and the European Medicines Agency (EMEA) estimated that more than 25,000 patients die each year in Europe, Iceland, and Norway as the result of an infection caused by multi-resistant bacteriaHow do bacteria become resistant to antibioticsAntibiotic resistance
Infections caused by antibiotic-resistant bacteria are increasing steadily worldwide in hospitals as well as in the community. These infections often have more severe outcomes than those caused by so called "sensitive" bacteria. As a consequence, they also require more expensive second-line treatments as well as a more careful and costly follow-up care for patients.
?

Bacteria can become resistant to some antibiotics: (i) innately or (ii) due to genetic changes that allow them to escape the effects of antibiotics to which they are usually sensitive.
(2). The same report estimated that in 2007, these infections accounted for a total annual cost of almost 1.5 billion euros in Europe (considering direct and indirect costs related to additional hospital days, ambulatory care, and decreased productivity: sick leave, death).

The specific situation in low-income countriesLow-income countries
The World Bank is a vital source of financial and technical assistance to developing countriesDeveloping country
This term is generally used to describe a nation with a low level of material well-being. Since no single definition of the term developing country is recognized internationally, the levels of development may vary widely within so-called developing countries. Some developing countries have high average standards of living.

The World Bank classifies all low- and middle-income countries as developing but notes, "The use of the term is convenient; it is not intended to imply that all economies in the group are experiencing similar development or that other economies have reached a preferred or final stage of development. Classification by income does not necessarily reflect development status".
around the world. It is not a bank in the common sense. It is made up of two unique development institutions owned by 187 member countries: the International Bank for Reconstruction and Development (IBRD) and the International Development Association (IDA). Each institution plays a different but collaborative role in advancing the vision of inclusive and sustainable globalization. The IBRD aims to reduce poverty in middle-income and creditworthy poorer countries, while the IDA focuses on the world's poorest countries.

For operational and analytical purposes, the World Bank's main criterion for classifying economies is gross national income (GNI) per capita. Based on its annual GNI per capita, every economy is classified as low-income, middle income (lower and upper middle income) or high income.
(3 & 4)

Neonatal infections: some figures

It is estimated that over 80% of the current world's population live in developing countriesDeveloping country
This term is generally used to describe a nation with a low level of material well-being. Since no single definition of the term developing country is recognized internationally, the levels of development may vary widely within so-called developing countries. Some developing countries have high average standards of living.

The World Bank classifies all low- and middle-income countries as developing but notes, "The use of the term is convenient; it is not intended to imply that all economies in the group are experiencing similar development or that other economies have reached a preferred or final stage of development. Classification by income does not necessarily reflect development status".


Compared to the total of 60 million annual deaths worldwide, over 10 million children under 5 years old die each year, of which 8 million die before their 1st birthday. Almost 99% of these infant deaths are observed in developing countriesDeveloping country
This term is generally used to describe a nation with a low level of material well-being. Since no single definition of the term developing country is recognized internationally, the levels of development may vary widely within so-called developing countries. Some developing countries have high average standards of living.

The World Bank classifies all low- and middle-income countries as developing but notes, "The use of the term is convenient; it is not intended to imply that all economies in the group are experiencing similar development or that other economies have reached a preferred or final stage of development. Classification by income does not necessarily reflect development status".
with the majority (90%) focused in only 42 countries mainly localized in sub-Saharan Africa and in southern Asia (Black RE et al, 2003, lancet) (Stein CE et al, 2004, Semin Pediatr Infect Dis).

The neonatal period represents only the first 4 weeks of life. However, 4 million children annually die during this critical period in both the community and hospitals, with three quarters of these deaths occurring during the first week of life alone (Lawn JE et al, 2005, Lancet) (Zaidi AK et al, 2005, Lancet).

The WHO estimates that 36% of neonatal mortality can be directly attributed to severe infections


including: septic states and pneumonia [26%], diarrhoea [3%], and tetanus [7%].

In the most deprived regions, the rate of neonatal mortality can exceed 50% (versus 4% in developed countries) while the proportion of deaths attributable to severe infections can be as high as 50%.

The problematic use of antibiotics: an amplification factor of the threat

The way antibiotics are used, or misused, and the inter-individual transmission of bacteria play a central role in the development and spread of bacterial resistance to antibiotics. Because these risk factors are highly prevalent in low-income countriesLow-income countries
The World Bank is a vital source of financial and technical assistance to developing countriesDeveloping country
This term is generally used to describe a nation with a low level of material well-being. Since no single definition of the term developing country is recognized internationally, the levels of development may vary widely within so-called developing countries. Some developing countries have high average standards of living.

The World Bank classifies all low- and middle-income countries as developing but notes, "The use of the term is convenient; it is not intended to imply that all economies in the group are experiencing similar development or that other economies have reached a preferred or final stage of development. Classification by income does not necessarily reflect development status".
around the world. It is not a bank in the common sense. It is made up of two unique development institutions owned by 187 member countries: the International Bank for Reconstruction and Development (IBRD) and the International Development Association (IDA). Each institution plays a different but collaborative role in advancing the vision of inclusive and sustainable globalization. The IBRD aims to reduce poverty in middle-income and creditworthy poorer countries, while the IDA focuses on the world's poorest countries.

For operational and analytical purposes, the World Bank's main criterion for classifying economies is gross national income (GNI) per capita. Based on its annual GNI per capita, every economy is classified as low-income, middle income (lower and upper middle income) or high income.
, these countries might be particularly vulnerable to the threat of resistance.



In low-income countriesLow-income countries
The World Bank is a vital source of financial and technical assistance to developing countriesDeveloping country
This term is generally used to describe a nation with a low level of material well-being. Since no single definition of the term developing country is recognized internationally, the levels of development may vary widely within so-called developing countries. Some developing countries have high average standards of living.

The World Bank classifies all low- and middle-income countries as developing but notes, "The use of the term is convenient; it is not intended to imply that all economies in the group are experiencing similar development or that other economies have reached a preferred or final stage of development. Classification by income does not necessarily reflect development status".
around the world. It is not a bank in the common sense. It is made up of two unique development institutions owned by 187 member countries: the International Bank for Reconstruction and Development (IBRD) and the International Development Association (IDA). Each institution plays a different but collaborative role in advancing the vision of inclusive and sustainable globalization. The IBRD aims to reduce poverty in middle-income and creditworthy poorer countries, while the IDA focuses on the world's poorest countries.

For operational and analytical purposes, the World Bank's main criterion for classifying economies is gross national income (GNI) per capita. Based on its annual GNI per capita, every economy is classified as low-income, middle income (lower and upper middle income) or high income.
, the use of antibiotics is often dangerously unregulated and disorganized. This includes the inconsistent quality of the molecules used due to the circulation of counterfeit medications (Kelesidis T et al, 2007, J Antimicrob Chemother) and the poor compliance to prescribed treatments due to the deprived background of the patients receiving them (treatment and/or reduced doses) (Okeke IN et al, 1999, Emerg Infect Dis). In addition, there is the possibility of accessing treatment, without medical prescription, from parallel markets where drug delivery is completely uncontrolled and unregulated.

The lack of hygiene and substandard living conditions linked to deprived backgrounds as well as the increase in the number of immunosuppressed individuals due to the HIV pandemic may constitute other factors promoting the emergence and dissemination of resistant bacteria in these countries (Okeke IN et al, 1999, Emerg Infect Dis).

Antibiotic resistance in the low-income countriesLow-income countries
The World Bank is a vital source of financial and technical assistance to developing countriesDeveloping country
This term is generally used to describe a nation with a low level of material well-being. Since no single definition of the term developing country is recognized internationally, the levels of development may vary widely within so-called developing countries. Some developing countries have high average standards of living.

The World Bank classifies all low- and middle-income countries as developing but notes, "The use of the term is convenient; it is not intended to imply that all economies in the group are experiencing similar development or that other economies have reached a preferred or final stage of development. Classification by income does not necessarily reflect development status".
around the world. It is not a bank in the common sense. It is made up of two unique development institutions owned by 187 member countries: the International Bank for Reconstruction and Development (IBRD) and the International Development Association (IDA). Each institution plays a different but collaborative role in advancing the vision of inclusive and sustainable globalization. The IBRD aims to reduce poverty in middle-income and creditworthy poorer countries, while the IDA focuses on the world's poorest countries.

For operational and analytical purposes, the World Bank's main criterion for classifying economies is gross national income (GNI) per capita. Based on its annual GNI per capita, every economy is classified as low-income, middle income (lower and upper middle income) or high income.
: a "spot-light syndrome"?


The problem of bacterial infections in low-income countriesLow-income countries
The World Bank is a vital source of financial and technical assistance to developing countriesDeveloping country
This term is generally used to describe a nation with a low level of material well-being. Since no single definition of the term developing country is recognized internationally, the levels of development may vary widely within so-called developing countries. Some developing countries have high average standards of living.

The World Bank classifies all low- and middle-income countries as developing but notes, "The use of the term is convenient; it is not intended to imply that all economies in the group are experiencing similar development or that other economies have reached a preferred or final stage of development. Classification by income does not necessarily reflect development status".
around the world. It is not a bank in the common sense. It is made up of two unique development institutions owned by 187 member countries: the International Bank for Reconstruction and Development (IBRD) and the International Development Association (IDA). Each institution plays a different but collaborative role in advancing the vision of inclusive and sustainable globalization. The IBRD aims to reduce poverty in middle-income and creditworthy poorer countries, while the IDA focuses on the world's poorest countries.

For operational and analytical purposes, the World Bank's main criterion for classifying economies is gross national income (GNI) per capita. Based on its annual GNI per capita, every economy is classified as low-income, middle income (lower and upper middle income) or high income.
is magnified by the emergence and spread of bacteria that are resistant to antibioticsAntibiotic resistance
Infections caused by antibiotic-resistant bacteria are increasing steadily worldwide in hospitals as well as in the community. These infections often have more severe outcomes than those caused by so called "sensitive" bacteria. As a consequence, they also require more expensive second-line treatments as well as a more careful and costly follow-up care for patients.
, including both Gram positive (Staphylococcus aureus and Streptococcus pneumoniae) and Gram negative (Haemophilus influenzae, enterobacteria) strains (Okeke IN et al, 2005, Lancet Infect Dis). Furthermore, some of these bacteria have become multiresistant, notably to some of the newest antibiotics.

famille


In contrast with "rich countries" where the progression of resistance is carefully monitored and actively combated, the current situation in developing countriesDeveloping country
This term is generally used to describe a nation with a low level of material well-being. Since no single definition of the term developing country is recognized internationally, the levels of development may vary widely within so-called developing countries. Some developing countries have high average standards of living.

The World Bank classifies all low- and middle-income countries as developing but notes, "The use of the term is convenient; it is not intended to imply that all economies in the group are experiencing similar development or that other economies have reached a preferred or final stage of development. Classification by income does not necessarily reflect development status".
is insufficiently documented. Indeed, epidemiological data on the incidence of these infections and their consequences are fragmented and records incomplete.

Currently, conditions are optimal for the emergence, diffusion, and unfavourable prognosis of antibiotic-resistant bacterial infectionsAntibiotic resistance
Infections caused by antibiotic-resistant bacteria are increasing steadily worldwide in hospitals as well as in the community. These infections often have more severe outcomes than those caused by so called "sensitive" bacteria. As a consequence, they also require more expensive second-line treatments as well as a more careful and costly follow-up care for patients.
in developing countriesDeveloping country
This term is generally used to describe a nation with a low level of material well-being. Since no single definition of the term developing country is recognized internationally, the levels of development may vary widely within so-called developing countries. Some developing countries have high average standards of living.

The World Bank classifies all low- and middle-income countries as developing but notes, "The use of the term is convenient; it is not intended to imply that all economies in the group are experiencing similar development or that other economies have reached a preferred or final stage of development. Classification by income does not necessarily reflect development status".
. However, compared with other severe issues such as malnutrition, malaria, and AIDS, the problem of resistance is still considered to be marginal. Furthermore, there is no evidence that the national or international health authorities are sufficiently aware of the severity of this problem to invest in measures to: (i) control the emergence of new mechanisms of resistance, (ii) limit the spread of resistant bacteria, and (iii) reduce their impact on human health.

It should be noted that the absence of local and national data on the resistance of the key pathogens in developing countriesDeveloping country
This term is generally used to describe a nation with a low level of material well-being. Since no single definition of the term developing country is recognized internationally, the levels of development may vary widely within so-called developing countries. Some developing countries have high average standards of living.

The World Bank classifies all low- and middle-income countries as developing but notes, "The use of the term is convenient; it is not intended to imply that all economies in the group are experiencing similar development or that other economies have reached a preferred or final stage of development. Classification by income does not necessarily reflect development status".
is an impediment to patient management and to updated local treatment recommendations. Current international data allow only a very partial and delayed surveillance of emergence phenomena. This is a major obstacle for public health decision makers and for the mobilization of resources needed to take action. Indeed, only solid and well-organised epidemiological surveillance can address these issues, allowing the containment of resistance at the local, national, and international levels (MacPherson DW et al, 2009, Emerg Infect Dis). This work is essential. By failing to take action, we risk remaining in a state of ignorance and falling victim to the "spot-light syndrome" which is to say focusing only on what has already been 'illuminated' through previous research at the expense of what has not. Neglecting the consequences of antibiotic resistanceAntibiotic resistance
Infections caused by antibiotic-resistant bacteria are increasing steadily worldwide in hospitals as well as in the community. These infections often have more severe outcomes than those caused by so called "sensitive" bacteria. As a consequence, they also require more expensive second-line treatments as well as a more careful and costly follow-up care for patients.
in these countries now could prevent the necessary consideration of this potential threat, ultimately leading to the discovery of a much bigger risk in the future.