Antibiotic Resistance 2013: The Antibiotics Development Pipeline And Strategies To Combat Antibiotic Resistance

Background

In Europe, 25,000 people die every year from drug-resistant infections and in 2009 there were 440,000 new cases of MDR tuberculosis, in 69 countries. These figures, and rising resistance levels seen in global surveillance programmes, show that antibiotic resistance has reached a critical point, as human and economic costs escalate. Many pathogens are now completely resistant to beta lactam antibiotics and MDR resistant Gonorrhoeal strains have emerged.

Resistance is a familiar problem in drug therapy, however there are unique aspects to antibiotic resistance in bacterial pathogens. This is because bacteria have evolved genetic and phenotypic attributes, which specifically enable them to withstand antibiotics, which they produce naturally. In consequence, bacteria have established a diverse pool of genes (the "resistome") that protect them against antibiotics used therapeutically, to target them. Killing pathogens is the goal of antibiotic therapy, but there is now a need to extend the capabilities of anti-bacterial therapies; to develop drugs that both destroy pathogens and also undermine resistance mechanisms in more effective ways.

Antibiotic resistance is now a global healthcare threat and today's armoury of antibiotics is increasingly limited. For some pathogens, the choice of available drugs is now greatly reduced. Increasing mortality from infections caused by resistant strains, and the strong link between resistant pathogens and increasing levels of hospital-acquired infections, together with escalating healthcare costs, have put antibiotic resistance at the top of the healthcare agenda.Despite its importance, pathogenomics (genome research on pathogenic microorganisms) is still at an early stage in its development, compared to human genome research. While bacterial genomes and phenotypes are being mapped, much less information is available on the horizontal spread of virulence genes across bacterial populations, an area that has fundamental relevance to keeping pace with the emergence of new resistant strains and the therapeutic strategies that can be used to target them. However, important initiatives are moving forward, notably the ERA-NET Pathogenomics programme and the development of the LLNL database.According to the US Centers for Disease Control and Prevention, 1.7 million patients per year in the US acquire an infection while in hospital, resulting in 99,000 (5.8%) deaths. In 1992, deaths from hospital-acquired infections in the US were 13,300, showing a 670% increase over a decade, equivalent to around a 20% annual growth during that time. The CDC also report that 70% of bacteria responsible for hospital-acquired infections are resistant to at least one of the antibiotics that were once used to treat them.In a report from the US state of Pennsylvania, state-wide hospitals reported 19,154 cases in which patients acquired an infection while staying in hospital, a rate of 12.2 cases per 1000 patients. The hospital costs associated with this patient group averaged $185,260 per patient, giving overall hospital costs of around $3.5 billion. By comparison, hospital costs for patients who did not acquire an infection were $32,389, around 17% of that seen in the case of patients who acquired an infection.In the US, it is reported that between 50–60% of all hospital-acquired infections are caused by antibiotic resistant bacteria. While little has been published on the relationship between antibiotic resistance and subsequent infection rates and prevalence, increases in both are an inevitable consequence of longer treatment times (durations of infection), due to antibiotic resistance. Also, the more time that is required to eradicate a pathogen from a patient, the higher the probability the pathogen will spread, particularly within the hospital environment, where patients and healthcare workers are in close proximity.Based on these figures, estimates of the cost of hospital-acquired infections, as a proportion of the general population, suggest a figure of $28.0 million/million of general population in the UK and $22.3 million/million of population in the US. The average of these two figures is approx $25 million/million of general population. Based on this average figure, hospital-acquired infections in the USA, Canada, Australia, Japan and Europe (population = 1.3 billion) is approximately $32.5 billion.

Surveillance

Surveillance studies by The European Antimicrobial Resistance Surveillance System (EARSS) in Europe, by the Active Bacterial Core surveillance (ABCs) Project in the US and by China's National Center for Antimicrobial Resistance, show steadily increasing levels of antibiotic resistance in 35 countries, amongst all human pathogen groups.

EARSS is a European surveillance network and collects antibiotic susceptibility/resistance data on six major pathogens, that cause invasive infections. These are Streptococcus pneumoniae, Staphylococcus aureus, Enterococci, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. In surveillance studies carried out since 2001, isolate data from over 900 laboratories serving 1400 hospitals in up to 28 countries, have been evaluated.

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