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  • The antibiotic resistance challenge

    A global impact

    A global impact

    Infectious diseases are caused by microorganisms, and for many of them, we rely on effective antibiotics for their treatment. Antibiotic resistance as it refers to bacteria means that antibiotics are no longer effective against these organisms. Infectious diseases which were treated by antibiotics in the 1960s (such as tuberculosis, gonorrhoea or pneumonia) may fail to respond to treatment today because of resistance. In serious infections, like surgery-related infections, meningitis and bloodstream infections (sepsis), this lack of response to antibiotics can quickly lead to death because of inadequate treatment options.

     

    Colistin is a last-resort antibiotic, used when other antibiotics fail. In 2015, a new and highly-mobile form of resistance to colistin was detected in a pig in China.(74) Called MCR-1, it was subsequently found in humans and food samples in several countries throughout the world,(75) highlighting the importance of improved surveillance efforts in humans, animals and the environment.

     

    In early 2016, a second colistin resistance gene, spreading even faster than MCR-1, was detected in bacteria from calves and piglets(76). The rapid emergence and spread of these forms of resistance were instrumental in placing antibiotic resistance on the agenda of the UN General Assembly in 2016.

     

    In 2017, just 2 years after the first report of plasmid-encoded colistin resistance, a total of four variants of the MCR gene have been identified. The first occurences of mcr-3 gene were identified in patients in Denmark, as well as in pigs in Spain. The fourth variant – mcr-4 – has been identified in pig samples from Italy, Spain and Belgium(97)(98), and a few months later in patients in Italy affected by gastroenteritis(105). This led several countries to ban the use of colistin in livestock.

     

    The use of powerful new tools such as Whole Genome Sequencing and the institution of national surveillance programs has significantly advanced the identification of these variants.

     

    A publication on Modern Colistin Resistance (MCR), co-authored by bioMérieux R&D and Medical Affairs teams, focuses on the medical and diagnostic consequences of emerging colistin resistance, and proposes pathways toward adequate diagnostics for timely detection of both asymptomatic carriage and infection.(91)

     

    Antibiotic resistance has also led to the resurgence of certain illnesses. In 2016, 10.4 million people fell ill with tuberculosis, and 1.7 million died from the disease. Multidrug-resistant TB (MDR-TB) remains a public health security threat, as WHO estimates that there were 600 000 new cases with resistance to rifampicin – the most effective first-line antibiotic - of which 490 000 people exhibited tuberculosis with multiple forms of resistance to drugs.(23)

     

    The Global Point Prevalence Survey of Antimicrobial Consumption and Resistance (GLOBAL-PPS) uses the ESAC Point Prevalence Surveillance method of data collection to monitors global rates of antimicrobial utilization and resistance in hospitalized patients. bioMérieux is the unique sponsor of the GLOBAL-PPS initiative.

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    Infections caused by important antibiotic-resistant bacteria (like vancomycin-resistant enterococci, carbapenem-resistant Enterobacteriaceae, multidrug-resistant Pseudomonas and Acinetobacter) are increasing worldwide, with limited alternative treatments available. The so-called ESKAPE bacteria pose the greatest threat – especially in healthcare settings (see HEALTHCARE-ASSOCIATED INFECTIONS) – because they rapidly acquire resistance to several classes of antibiotics. The ESKAPE bacteria include Enterococcus faecium, Staphylococcus aureus, Klebsiella species, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species.

    Most frequent infections caused by Escherichia coli

    Escherichia coli is part of the normal intestinal flora in humans and animals. But when these bacteria appear in areas where they should not be present or when a specific disease-causing strain starts circulating between animals, food and humans, it can cause a variety of infections:

    • Community and hospital-acquired urinary tract infections.
    • Bloodstream infections and intra-abdominal infections such as peritonitis.
    • Meningitis in neonates.
    • Food-borne infections. For instance, the 0157 strain of E. coli is known for its ability to secrete the Shiga toxin and cause fever, nausea, vomiting, stomach cramps and potentially fatal diarrhoea.

    E. coli is increasingly resistant to antibiotics such as quinolones and 3rd generation cephalosporins.

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    Most frequent infections caused by Streptococcus pneumoniae

    Streptococcus pneumoniae — also known as “pneumococcus” — is commonly found in the nose and pharynx without causing disease. Therefore, the general population is responsible for much of its transmission to the older, younger or debilitated members of the community, in whom it may cause disease.

    • Streptococcus pneumoniae is the leading cause of community-acquired pneumonia, which is among the main killers of children under 5 years of age (about 11% of all deaths in this age group globally, which translate into 820,000 fatalities per year).
    • Streptococcus pneumoniae can also cause self-limiting infections such as otitis, or more severe infections such as meningitis, with permanent residual symptoms and high associated mortality.
    • It can also lead to food poisoning outbreaks

    Streptococcus pneumoniae is increasingly resistant to penicillin.

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    Most frequent infections caused by Staphylococcus aureus

     

    The bacterium Staphylococcus aureus — which can turn into the infamous “MRSA” (methicillin-resistant S. aureus) — is part of the normal microbial flora of the skin and nests in about 30% of human noses. Depending on the type of strain and the immune system of its host, it can cause skin, soft tissue, bone and even bloodstream infections.

    • In hospitals, it is the most common cause of surgical wound infections.
    • In livestock, it affects the skin of animals causing a variety of illnesses such as mastitis, a common infection of the mammary glands in dairy cows.

    Staphylococcus aureus is increasingly resistant to antibiotics such as methicillin and vancomycin.

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    Community-acquired or hospital-acquired infections (see HEALTHCARE-ASSOCIATED INFECTIONS) can affect any person at any age. Individuals at highest risk for these infections are those with impaired immune systems (like newborns, individuals receiving chemotherapy, HIV-infected people, and other persons with immune diseases) and those who have undergone invasive medical procedures (like complex surgery, cardiac operations, organ transplants and joint replacements, and placement of indwelling medical devices).

    Primary care doctors and specialists rely on effective antibiotics to treat a vast array of infections, from urinary tract or gastrointestinal infections (see FOODBORNE AND WATERBORNE INFECTIONS), to pneumonia or skin infections.  More than 1 million sexually transmitted infections are acquired every day worldwide, and can have a major impact on the health of newborns.(106)

    It is also worth mentioning the importance of antibiotics to treat the complications or treatment side-effects associated with many common diseases, such as diabetes, arthritis and cancer. For instance, doctors rely on effective antibiotics to treat infected foot ulcers, a condition which may affect 1 in 4 of the 400 million people living with diabetes.(25)

    Bloodstream infections are one of the most severe forms of infection and can be caused by a large number and variety of bacteria. They can emerge as a complication of other types of infection and rapidly turn into a medical emergency known as sepsis, a leading cause of death in the world. The 70th World Health Assembly adopted a resolution to address the growing burden of sepsis, with 31 million cases and 6 million deaths recorded annually.

    The growth of antibiotic resistance has increased the fatality rate of this syndrome. The majority of bloodstream infections originate from urinary tract infections or pneumonia. The rapid diagnosis of sepsis is crucial for starting an effective and timely antibiotic prescription. This urgent recognition of sepsis and its source, along with the proper supportive care and the correct choice of antibiotic therapy, are critical for decreasing the morbidity and mortality associated with this life-threatening condition.

     

     

     

    Find out more about Sepsis Management 

    Procalcitonin measurements can help diagnose blood stream infections, and assess the severity and prognosis of the infection. This measurement helps to differentiate bacterial infections from viral ones and helps physicians come to rational clinical decisions and optimize patient management. The early detection of an elevated procalcitonin level in patients with suspected bacterial infections allows earlier antibiotic treatment, and gives information about the severity and prognosis of an infection. Procalcitonin measurements also contribute to rational decisions on whether to continue or stop antibiotics, thus improving patient care and decreasing antibiotic misuse and the potential for the development of resistance.

    VIDAS® B·R·A·H·M·S PCT™ is an automated 20-minute test used for the rapid detection of the level of procalcitonin in human serum or plasma from patients suspected of sepsis.

    Lower respiratory tract infections are the leading infectious cause of death (the fifth-leading cause of death overall) and the second-leading cause of disability-adjusted life-years. At the global level, the burden of LRIs has decreased dramatically in the last 10 years, especially in children younger than 5 years, although the burden in people older than 70 years has increased.(26) These infections can be caused by viruses (for example: influenza virus, respiratory syncytial virus) or bacteria. Antibiotics have no effect against viruses and are often unnecessarily prescribed because of a mistaken clinical diagnosis, or due to the suspicion of a bacterial infection being present. Some bacterial infections can be recognized and subsequently treated using simple and rapid diagnostic tests (CRP, Legionella, Streptococcus pneumoniae). Furthermore, current “multiplex” syndromic lab tests are now able to simultaneously detect the presence of common viruses and bacteria in a single respiratory sample in approximately one hour, assisting the clinician in rapidly determining the cause of such an infection. This knowledge is crucial in deciding whether antibiotics are appropriate and, if indicated, which antibiotics are optimal. This data, along with clinical information and an evidence-based approach, can decrease the overall use of antibiotics, their inappropriate use and the subsequent antibiotic resistance which we are trying to avoid.

     

    bioMérieux solutions related to respiratory tract infections

    BIONEXIA® Influenza A+B

    BIONEXIA® Legionella

    FILMARRAY®, FILMARRAY® 2.0 and FILMARRAY®Torch

    These infections may be caused by bacteria, viruses, and parasites. Bacterial foodborne infections are usually caused by specific strains of Salmonella, Listeria, E. coli, Campylobacter, Shigella, etc. Many of these may require effective antibiotics for appropriate patient treatment. Beyond causing diarrhoeal disease, foodborne infections can even lead to death. Each year, foodborne pathogens cause approximately 9.4 million illnesses in the United States, resulting in an economic burden of over $15.5 billion (2013 dollars).(4)

    For instance, Salmonella strains, which can be found in the intestines of livestock such as poultry and pigs, often cause gastroenteritis. One global estimate suggests that there are around 94 million cases of gastroenteritis every year caused by Salmonella alone, resulting in 155 000 deaths. The majority of the disease burden from Salmonella is in the African, South-East Asian and Western Pacific Regions. Some strains (such as Salmonella typhi and para-typhi which cause “typhoid fever”, a serious condition) are particularly invasive.

    The CDC and ECDC are now working closely with food and veterinary agencies, respectively with FDA, USDA and EFSA, to place these organisms under surveillance to monitor antibiotic resistance levels in animals, food and in humans. Surveillance of antibiotic use is also carried out both in humans and animals in an attempt to reduce antibiotic use in both sectors.

    Resistance is increasingly observed in travel-associated bacterial infections as well. This is the case for Salmonella typhi and Shigella, whose resistance to ciprofloxacin is becoming a threat for the treatment of these infections.(27)

    Moreover, colonization with multi-drug resistance organisms (MDRO) after travel to certain areas may exceed 50%.(28)

     

    bioMérieux’s solutions for foodborne and waterborne infections

    Our solutions include culture media, both conventional and chromogenic (such as CHROMID® Salmonella, SMAC for E.coli 0157).

    In addition, the FILMARRAY® GI (Gastrointestinal) multiplex PCR panel is able to simultaneously detect the most common causes of gastrointestinal diseases including 15 bacteria, five viruses and four parasites within 1 hour, directly from stool specimens.