The World Health Organization (WHO) launched a global campaign Tuesday to curb the spread of antibiotic resistant germs through safer and more effective use of the life-saving drugs.
Key facts
- Antibiotic resistance is one of the biggest threats to global health, food security, and development today.
- Antibiotic resistance can affect anyone, of any age, in any country.
- Antibiotic resistance occurs naturally, but misuse of antibiotics in humans and animals is accelerating the process.
- A growing number of infections – such as pneumonia, tuberculosis, gonorrhoea, and salmonellosis – are becoming harder to treat as the antibiotics used to treat them become less effective.
- Antibiotic resistance leads to longer hospital stays, higher medical costs and increased mortality.
The UN health agency said it had developed a classification system listing which antibiotics to use for the most common infections and which for the most serious ones, which drugs should be available at all times, and which should be used as a last resort only.
The aim is to prevent antibiotic resistance, which happens when bugs become immune to existing drugs, rendering minor injuries and common infections potentially deadly.
Such resistance can develop naturally, but overuse and misuse of the drugs dramatically speeds up the process.
“Antimicrobial resistance is an invisible pandemic,” WHO assistant director-general for access to medicines, Mariangela Simao, said in a statement.
“We are already starting to see signs of a post-antibiotic era, with the emergence of infections that are untreatable by all classes of antibiotics,” she said.
Discovered in the 1920s, antibiotics have saved tens of millions of lives by defeating bacterial diseases such as pneumonia, tuberculosis and meningitis.
But over the decades, bacteria have learned to fight back, building resistance to the same drugs that once reliably vanquished them – turning into so-called “superbugs”.
‘Urgent’ health risk
The WHO campaign pointed to numbers from the Organisation for Economic Co-operation and Development estimating that some 2.4 million people could die over the next 30 years in Europe, North America and Australia due to superbug infections.
According to a recent report by the International Coordination Group on Antimicrobial Resistance, more than 50 percent of antibiotics in many countries are used inappropriately.
This includes antibiotics, which work only against bacterial infections, prescribed to treat viruses.
At the same time, many low- and middle-income countries see vast gaps in access to effective and appropriate antibiotics.
Nearly one million children die each year from pneumonia that could have been treated if they had access to antibiotics, WHO pointed out.
The UN health agency’s new classification, which it dubbed AWaRe, splits antibiotics into three categories: Access, Watch and Reserve.
The campaign aims to have drugs in the basic Access category make up at least 60 percent of total antibiotic consumption, while reducing use of drugs in the other categories, to be reserved for cases where other antibiotics have failed.
Using antibiotics in the Access group lowers the risk of resistance because they are so-called “narrow-spectrum” drugs, meaning they target a specific bacteria rather than several, the WHO explained.
They are also less costly, it said.
But the body warned that only 65 countries in the world collect data on their antibiotic use, and fewer than half of those – almost all in Europe – meet the 60-percent goal.
“Antimicrobial resistance is one of the most urgent health risks of our time and threatens to undo a century of medical progress,” WHO chief Tedros Adhanom Ghebreyesus said in Tuesday’s statement.
“All countries must strike a balance between ensuring access to life-saving antibiotics and slowing drug resistance by reserving the use of some antibiotics for the hardest-to-treat infections,” he said.
Antibiotic resistance – a serious global problem
Antibiotics have revolutionized medicine, including improving orthopaedic surgical and implant outcomes, in many respects and have transformed human health and well-being for the better.
Before the use of antibiotics, the fatality rate for Staphylococcus aureus (S. aureus) bacteremia was high and most wound infections were treated by amputation; for instance, ~70% of amputations in World War I were result of wound infections.1
The introduction of antibiotics has dramatically improved the fate of infected patients and has changed the way various diseases and surgical procedures are treated.
The ability of antibiotics to treat and cure infection has dramatically reduced the number of incidences of infection, significantly improving the quality of life for numerous patients, reducing childhood mortality, increasing life expectancy, and saving numerous lives.
Antibiotics were first studied in the late 1800s and it was in early 1900s that penicillin was discovered.
The value of using penicillin during and after orthopaedic surgeries was first highly appreciated during World War II when treating casualties from the War.
The success of penicillin was followed by the development of a variety of new antibiotics. Currently, cephalosporins (e.g., cefazolin, cefalotin), aminoglycosides (e.g., gentamicin, tobramycin, amikacin), glycopeptide antibiotics (e.g., vancomycin, teicoplanin), and quinolones (e.g., ciprofloxacin, ofloxacin) have been extensively used in orthopaedic surgeries to prevent or treat infections.
Unfortunately, the discovery and increasingly widespread use (especially the misuse) of antibiotics have led to the rapid appearance of antibiotic resistant strains today; more and more infections are caused by microorganisms that fail to respond to conventional treatments.
Meanwhile, the discovery and development of antibiotics have been declining rapidly over the past several decades; for instance, 16, 14, 10, and 7 new antibiotics were approved during 1983–1987, 1988–1992, 1993–1997, and 1998–2002, respectively, while only 5 and 2 were approved during 2003–2007 and 2008–2012, respectively.2
This decline was due to decreasing antibiotic research and development in major pharmaceutical companies;2 investment in new antibiotic development has been hampered by the uncertain lifecycles (associated with antibiotic resistance development) of new antibiotic drugs and government regulations affecting the pace of translational exploitation.3
The approximate timeline for the introduction of multiple major antibiotics and the subsequent emergence of clinically significant bacteria antibiotic resistance is shown in Fig. 1.4
Following the introduction of sulfonamides and penicillin around 1937 and 1940, resistance to sulfonamides and penicillin were reported within a few years (around 1945).
Resistance to tetracycline, streptomycin, and chloramphenicol was found in the 1950s.
Methicillin was introduced in 1959 and methicillin resistant S. aureus (MRSA) was identified in 1961. MRSA has since become widespread in hospitals and, relatively recently, in numerous communities worldwide leading to the consideration of antibiotic resistance as a real threat to human health.
Linezolid and daptomycin were introduced in the 2000s and their resistance was reported within five years.
In fact, a report was given to the United Nations in 2016 concerning the significant consequences of antibiotic resistance to human health; this report represents only the second time in the history of the United Nations that threats to human health have been presented.
Fig. 1
Timeline showing the time between the introduction of an antibacterial and the development of clinically significant resistance. Reprinted with permission from 4.
Currently, the most notorious antibiotic resistant bacteria is S. aureus, and antibiotic resistant microorganisms including Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species have been identified as the so-called “ESKAPE” microorganisms which have caused significant morbidity and mortality.5
In the U.S., the Centers for Disease Control and Prevention (CDC) has also classified multidrug resistant (MDR) microorganisms into three different levels (i.e., threat levels of urgent, serious, and concerning).6
Among these MDR microorganisms, many of them have been reported in orthopaedic implant-associated infections including MRSA, vancomycin-resistant S. aureus (VRSA), multidrug-resistant Acinetobacter, extended spectrum β-lactamase producing enterobacteriaceae (ESBLs), and multidrug-resistant Pseudomonas aeruginosa.
Their resistance has a broad effect on treating and preventing infections (Table 1).7
The consequences of antibiotic resistance are very serious, and could present a significant impact on morbidity and mortality and lead to financial burdens for patients and public health systems, as described below:
Table 1
Effects of antibiotic resistance. Reprinted from reference,7 Clinical Microbiology and Infection, 22, Friedman ND, Temkin E, Carmeli Y. The negative impact of antibiotic resistance, 416–422. Copyright (2016), with permission from Elsevier.
| The effect | Examples |
|---|---|
| Morbidity and mortality | All-cause |
| Attributable to infection | |
| Increased length of hospital stay | |
| Increased length of mechanical ventilation | |
| Increased need for intensive care and invasive devices | |
| Excess surgery | |
| Functional decline and need for post-acute care | |
| Need for contact isolation | |
| Loss of work | |
| Increased resource utilization and cost | Hospital, intensive-care unit and post-acute care beds |
| Additional nursing care, support services, diagnostic tests and imaging | |
| Additional use of isolation rooms and consumables (gloves, gowns) | |
| Cost of targeted infection control programs including screening, isolation | |
| Guideline alterations | Loss of narrow-spectrum antibiotic classes |
| Altered empiric therapy regimens | |
| Use of agents with reduced efficacy | |
| Use of agents with increased toxicity | |
| Reduced hospital activity | Unit closures |
| Cancellation of surgery |
- Antibiotic resistance likely compromises the safety and efficacy of surgical procedures like implantation and transplantation that require the protection of antibiotics. It is estimated that between 38.7% and 50.9% of microorganisms causing surgical site infections are resistant to standard prophylactic antibiotics in the U.S.7
- Antibiotic resistance has a direct effect on treating infections. Patients (not orthopaedic specific) with infections caused by MDR microorganisms are generally at increased risk of worse clinical outcomes and death, and consume more health-care resources compared with similar infections caused by antibiotic susceptible strains.8 Approximately a two-fold increase in morbidity, mortality, and cost for patients with resistant versus susceptible infections has been reported in patients (not orthopaedic specific) who had clinical cultures positive for Enterobacter species.9 A two-fold higher risk of death was attributed to infections caused by carbapenem-resistant K. pneumoniae compared to infections caused by carbapenem-susceptible strains in adult patients with K. pneumoniae bacteremia.10Meanwhile, hospitals spend, on average, an additional $10,000–40,000 to treat a patient infected by resistant bacteria versus susceptible strains.11 According to the CDC, in the U.S. alone, antibiotic resistant bacteria cause at least 2 million infections, 23,000 deaths a year,6 and $55–70 billion per year in economic impact.12,13 In Europe, approximately 25,000 people die annually due to MDR bacterial infections, along with a 1.5 billion per year cost in the economy.14,15
- Antibiotic resistance may have negative effects on domesticated animals such as pets and farm animals.16
