“If we don’t address stewardship, we are doomed to failure.”
Ramanan Laxminarayan (Director of the Center for Disease Dynamics, Economics and Policy) - 2015
Antimicrobial stewardship is defined as a program which seeks to ensure that the right antibiotic is given to the right patient at the right time with the right dose and the right route, causing the least harm to the patient and future patients. In realistic terms, it is a multidisciplinary approach that aims to ensure that patients benefit from the most effective antibiotic treatments, while limiting the side effects and costs of unnecessary treatments.
Successful antimicrobial stewardship programs require a continued and diligent interaction between all levels of healthcare providers, including physicians, infectious disease specialists, infection control practicioners, nursing staff, pharmacists, microbiologists, pathologists, lab directors and healthcare administrators.
The core elements of antimicrobial stewardship programs include:
- Implementation of national and international guidelines and clinical pathways for the diagnosis and treatment of infectious diseases
- Limiting the use of antibiotics where not needed or not indicated
- Delivering the most appropriate antibiotic, with the correct dose established according to the type and site of infection, patient’s age, weight and clinical situation
- Switching antibiotics from parenteral to oral form as soon as possible
- Timely conversion to the most narrow antibiotic spectrum according to the organism susceptibility
- Use of the shortest effective antibiotic course and discontinuation of antibiotic courses as soon as possible
The leading factor in the emergence of antibiotic resistance is the inappropriate use of antibiotics in both humans and animals. Available data highlight a correlation between the use of antibiotics and resistance rates in a given country.(54) Even though detailed and reliable data remain unavailable for many parts of the world, it is clear that antibiotic resistance is as much an issue for emerging nations as it is for the developed world. As populations are mixing through tourism and migration, various microbes with their antibiotic resistance genes are spreading worldwide, implying the need for global coordinated efforts.(55)
A 2015 report entitled “The State of the World’s Antibiotics 2015” published by the CDDEP (Center for Disease Dynamics, Economics & Policy) stated that incentives have focused on the development of new antibiotics, but insufficient attention has been paid to conserving the effectiveness of our existing antibiotic arsenal. Global antibiotic stewardship in the broadest sense should make it possible not only to conserve the current effectiveness of existing antibiotics, but even to reclaim some of the effectiveness that has been lost through bacterial mutations.
According to report co-author and CDDEP Director Ramanan Laxminarayan, 80% of our global resources for controlling AMR should be focused on antimicrobial stewardship and no more than 20% on drug development, because no matter how many new drugs come out, they will all generate resistant bacterial mutants if we continue to misuse them. (Press conference, Sept 17, 2015).
Global consumption of antibiotics in human medicine rose by 36% between 2000 and 2010.(57) This general figure masks declining use in some countries and rapid growth in others. The combination of limited health-care systems and rising incomes to spend on drugs makes emerging countries especially susceptible to overconsumption. Brazil, Russia, India, China and South Africa accounted for three quarters of the global increase in demand for antibiotics between 2000 and 2010, while annual per-person consumption of antibiotics varied by more than a factor of 10 across all middle and high-income countries.(57)
Despite the ban of antibiotics as growth promoters for livestock in some countries, such as the member states of the EU, the total veterinary use of several classes of antibiotics has steadily increased in several countries. In 2010, the world used about 63,000 tons of antibiotics to raise cows, chickens and pigs.(58) Taking note of the surge in antibiotic resistance, some industries have pre-empted government decisions and made voluntary decisions to restrict the use of antibiotics. For instance, several food companies in the USA have recently decided to phase out the use of antibiotics which are important for human health in the farming of chickens. In France, following a ban by the pig industry of the use of 3rd and 4th generation cephalosporins, the consumption of those antibiotics decreased by 62% between 2010 and 2012.(59) It is widely accepted that improved disease prevention measures and reduced animal stress can avoid the need for antibiotics while enhancing animal welfare.
The use of antibiotics on crops is worth mentioning, even if total quantities remain low. Pears, apples and other rosaceous plants are vulnerable to “fire blight” (caused by the bacteria Erwinia amylovora). Broad-spectrum antibiotics (such as streptomycin or oxytetracycline), which are active against a wide variety of bacteria and resemble some antibiotics used for humans, are sometimes used on trees to prevent or treat infection by fire blight.(60)
Antibiotics save millions of human and animal lives worldwide every year, but in many cases they are misused or unnecessarily consumed. In developed countries, between 10 and 20 courses of antibiotics are prescribed to children before the age of 18 years.(61) Furthermore, it has been demonstrated that up to 50% of all antibiotics prescribed in human medicine are not needed or not prescribed appropriately.(2)
In 2017, new advice on which antibiotics to use for common infections and which to preserve for the most serious circumstances was among the additions to the WHO Model list of essential medicines. This list is used by many countries to increase access to medicines and guide decisions about which products they ensure are available for their populations. WHO experts grouped antibiotics used to treat 21 of the most common general infections into three categories: ACCESS, WATCH and RESERVE groups.
Healthcare providers have an essential role to play in the appropriate use of these drugs to contain the emerging antibiotic resistance problem. Rapid, high medical value diagnostics in conjunction with Antimicrobial Stewardship Programs can be used to support relevant decisions to withhold, de-escalate or stop antibiotic treatment earlier. Antimicrobial Stewardship Programs encourage rational prescribing of antibiotics and remindhealthcare workers – and their patients – of the consequences of antibiotic over-use and misuse. In fact, we all need to change our views on antibiotics and reconsider them as shared non-renewable resources, which must be preserved.
While the optimal approach to effective antimicrobial stewardship remains elusive and may vary significantly between settings, a wide array of studies and reviews from diverse healthcare contexts have demonstrated the positive impact of stewardship programs on limiting antibiotic resistance.(62)
The U.S. Center for Infectious Disease Research and Policy offers information and educational resources on antimicrobial stewardship practice, research and policy.
State-of-the-art guidelines and information are essential for antimicrobial stewardship programs.
In 2016, the Infectious Diseases Society of America and the American Thoracic Society published new guidelines recommending a shorter duration of antibiotic treatment in adults with two common hospital-acquired infections: ventilator-associated pneumonia and hospital-acquired pneumonia. Shortening the course of antibiotic treatment reduces the potential for antibiotic resistance, while maintaining the benefit of the treatment. The new guidelines also recommend that hospitals use antibiograms to determine the most appropriate treatment.
A WHO expert panel has updated the list of antibiotics considered most important to human medicine(85). Fluoroquinolones, macrolides, third-generation cephalosporins, glycopeptides and carbapenems are identified as the highest priority antibiotics to be preserved. The list is intended to support stewardship efforts, particularly in the context of animal farming.
- Establish a clear aim/vision that is shared by all stakeholders and that conveys a sense of urgency. Stewardship should be a patient safety priority.
- Seek management support, accountability and secure funding.
- Assemble a strong coalition including a multi-professional antimicrobial stewardship team with an influential clinical leader.
- Establish effective communication structures within your hospital.
- Start with core evidence-based stewardship interventions depending on local needs, geography and resources and set up measurement strategies to demonstrate their impact.
- Ensure that all healthcare staff are aware of the importance of hospital-based antimicrobial stewardship. Empower them to act and to support others using a range of effective advocacy tools.
- Ensure early or short-term wins and then consolidate success/gains while progressing with further change and innovation.
Source: “Practical Guide to Antimicrobial Stewardship in Hospitals”(63)
- In Europe, the use of antibiotics as alleged growth promoters for food-producing animals has been banned since 2006. But such a use for antibiotics is still allowed in many other countries.
- Antibiotics are still mistakenly used to treat viral infections, for which they have no effect.
- Antibiotic regimens are too often not followed as prescribed. When people stop taking their pills as symptoms clear up, it potentially allows resistant bacteria to develop.
- In some cases, antibiotics may be taken by patients as self-medication (for instance to treat upper respiratory tract infections, the majority of which are caused by viruses for which antibiotics are ineffective). This can also lead to generation of resistant bacteria.
- Access to antibiotics is too easy in many countries (“over the counter” without a medical prescription).
The increased consumption of antibiotics is also a cause of concern because a proportion of this quantity will eventually appear in the environment. This is because antibiotics are seldom fully metabolised, either by humans or by animals, and can show up in their urine and feces. In the case of livestock, antibiotics are usually administered orally in the feed, then they are only partially digested and appear in the feces which may be used as manure and then spread onto agricultural fields. These drug residues can leach into the soil, contaminating water resources and our food supply. A study has also shown that residues of tetracycline antibiotics have an unexpected effect on the development of many life forms and can potentially reduce the growth of plants.(64) Beyond the fact that antibiotic residues can cause allergic reactions, a major concern stems from these residues being present at relatively low concentrations, which facilitates the emergence of antibiotic-resistant bacteria during contact.
Other effects of antibiotics on humans
The nature and intensity of side effects caused by antibiotics vary considerably from one person to another. They depend on the class of antibiotic used, and on whether other drugs are being taken at the same time. Skin rashes, allergies, diarrhoea or an imbalance of the intestinal flora are among the most common side effects of antibiotics.(65)
In fact, bacteria are key components of our “inner and outer self”. Our digestive tract and our skin (including the mouth, nose, ears, etc.) are covered by trillions of bacteria which outnumber our own cells 10-fold. These bacteria, which live in close contact with us, are termed the “microbiota” or the “microbiome”. They weigh a total of approximately 1.5 kilograms and perform many functions vital to human health and survival: they digest food, produce anti-inflammatory chemicals and compounds, and train the immune system to distinguish “friend from foe”. In fact, they play so many key roles in our metabolism that some scientists compare the microbiota to an organ. In this view, the human body is a complex ecosystem including numerous collaborating and competing microbial species.(66) Many antibiotics may eradicate or alter the useful bacteria that help us metabolize food efficiently, keep our body surfaces and mucous membranes (mouth, nose, genital tract) healthy or maintain healthy skin. All of the effects of this change in the microbiome by antibiotics are not known, but many such consequences have been well-documented such as overgrowth of yeast or diarrhea
Clostridium difficile: a deadly side-effect
When a person takes antibiotics, the “good bacteria” present in our microbiome that offer some protection against infection can be destroyed. At that time, an individual in contact with Clostridium difficile (otherwise known as “C. difficile” or “C. diff”) can develop a potentially deadly form of diarrhea called “C. difficile infection” (CDI). The people receiving antibiotics who are most at risk include older adults in both acute care hospitals and long-term care facilities, patients in critical care units and individuals with an impaired immune system. In 2011, half a million Americans acquired CDI and the US Centers for Disease Control (CDC) estimated that it killed 15,000 of them.(67)
bioMérieux solutions for the management of C. difficile