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.
The actual number of deaths related to antibiotic resistance is unknown, since such information is usually missing from medical reports and death certificates. However, some key estimates available on the mortality induced by antibiotic resistance include:
- every 4 minutes, a person dies from an infection caused by bacteria which have become resistant to antibiotics (combined data from the EU, the USA and for children in India)(1),(2),(3)
- at least 25,000 patients in Europe and 23,000 patients in the USA die each year as a result of antibiotic-resistant infections.(1),(2)
- each year in the USA, methicillin-resistant Staphylococcus aureus (MRSA) causes an estimated 80,000 infections and 11,000 deaths.(2)
- almost 250,000 people each year require hospital care for Clostridium difficile (C. difficile) infections, and 14,000 patients die of a C.difficile infection annually. In most of these cases, the use of antibiotics was a major contributing factor leading to the illness.(2)
Colistin is a last-resort antibiotic, used when other antibiotics fail. In 2015, a form of resistance to colistin was detected in a pig in China.(74) The resistance gene involved can be exchanged quite easily between one species of bacteria and another. This gene, called MCR-1, was subsequently found in humans and food samples in several countries throughout the world.(75)
In early 2016, a second colistin resistance gene, spreading even faster than MCR-1, was detected in bacteria from calves and piglets(76). The alarming 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, leading to a global reconsideration of the use of colistin in livestock. The first mcr-3 gene cases were identified in patients using a national surveillance database in Denmark as well as in pigs in Spain, and mcr-4 has been identified in pig samples from Italy, Spain and Belgium(97)(98).
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. The case of colistin resistance has highlighted the importance of improved surveillance efforts in humans, animals and the environment.
A recent 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)
The economic impact of antibiotic resistance is difficult to calculate but a recent study has shown that:
- the total cost to the U.S. economy may be as high as $20 billion in excess direct healthcare costs.(22)
- additional costs to the U.S. society for lost productivity may be as high as $35 billion a year (2008 dollars).(22)
Antibiotic resistance has also led to the resurgence of certain illnesses such as tuberculosis, now considered as a “re-emerging” disease:
- in 2015, there were an estimated 1.4 million deaths attributable to tuberculosis worldwide, and 480,000 people were infected by drug-resistant strains.(23)
In its 2014 “Antimicrobial resistance global report on surveillance”, the WHO outlined the global situation regarding antibacterial, antiviral, antifungal and antiparasitic resistance. A look at the data available for 114 countries on the resistance of 7 pathogens to antibiotics reveals startling figures:
- at the global level, an average of 25% of Streptococcus pneumoniae strains are resistant to penicillin;
- in five out of the six WHO global regions, Escherichia coli resistance is over 50% for 3rd generation cephalosporins and quinolones which are often considered essential antibiotics for that type of infection;
- in three of the six WHO regions, 25% of Neisseria gonorrhoeae (a sexually transmitted bacteria) are resistant to 3rd generation cephalosporins which are supposed to be the treatment standard for this type of infection.(6)
The Global Point Prevalence Survey of Antimicrobial Consumption and Resistance (GLOBAL-PPS) uses the ESAC Point Prevalence Surveillance method of data collection to monitor global rates of antimicrobial utilization and resistance in hospitalized patients. The interim results of this unique global study, sponsored by bioMérieux, were presented in June 2015, during the 5th World HAI forum on antimicrobial resistance (see EDUCATION AND ADVOCACY TO TACKLE ANTIBIOTIC RESISTANCE). Further results were released in November 2015 and the final results were presented during the ECCMID 2016 (European Congress on Clinical Microbiology and Infectious Diseases).(24) Plans are underway to continue and expand this vast surveillance project for additional years and in more countries.
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.
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.
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.
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 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 to pneumonia or skin infections. Some bacteria have the ability to infect any part of the body (skin and soft tissues, lungs, bones, brain, etc.). Infections are not all equally dangerous: whereas urinary tract infections are rarely fatal, pneumonia has a high mortality rate (see RESPIRATORY TRACT INFECTIONS). Sexually transmitted bacterial infections such as chlamydia, gonorrhoea or syphilis affect almost half a billion people worldwide and can have a major impact on neonatal health.
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) Antibiotics are also vital for treating the complications of chemotherapy when given to cancer patients and essential for curing the infections occurring in immuno-compromized populations. Antibiotics are becoming more and more necessary for preventing and treating infections associated with our increasingly complex surgeries such as cardiac operations, organ transplants and joint replacements.
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. In Europe and the USA, bloodstream infections affect more people than cancer. In the USA alone, over 750,000 severe cases of sepsis occur every year, with an average annual cost of $16.7 billion.
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.
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.
Respiratory tract infections are, after ischaemic heart disease, the second largest contributor to years of life lost due to premature death.(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
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. Salmonella infections are usually acquired by the consumption of contaminated water or food of animal origin, such as undercooked meat, poultry, eggs or unpasteurized milk. Human or animal faeces, used as fertilizers in some countries and sometimes containing Salmonella, can contaminate the surface of fruits and vegetables and bacteria can also be transmitted in this way.
Resistance is also a concern with foodborne infections. The bacteria most frequently isolated from foodborne and other enteric infections have significantly contributed to the emergence and spread of resistance. As a consequence, resistance rates in Campylobacter, Salmonella and Shigella have dramatically increased, reaching the “serious” level of resistance defined by CDC and making the treatment of the most serious forms of infection much more challenging. 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.