Patients like the febrile child present with symptoms, not a diagnosis. Having appropriate diagnostic tools to identify diseases accurately can mean the difference between a patient receiving the care they need and receiving ineffective or unnecessary antibiotics, further contributing to AMR. Rapid diagnostic tests (RDTs) for malaria can help to differentially diagnose patients presenting with fever. While positive RDT results can allow for timely treatment with antimalarials, negative findings on these RDTs have been found in some situations to result in providers overprescribing antibiotics. Diagnostic tests can sometimes be more costly than empirically treating with antibiotics, without a diagnosis. Better use and availability of diagnostic tools are crucial in mitigating the overuse of antibiotics and de-escalating broad-spectrum antibiotics to more targeted antibiotic regimens. Appropriate use of antibiotics can also reduce economic costs through shorter hospital stays. Sometimes the laboratory equipment is not readily available where patients require such services. The Mini-Lab project, organized by Médecins sans Frontières (MSF), seeks to “design and produce a small-scale, autonomous, transportable clinical bacteriology laboratory which is affordable and above all suited to the MSF’s fields of intervention.” Even where the equipment might be made available, technicians with the skill to read the microbiology culture and sensitivity results may not be. Along these lines, MSF developed the Antibiogo app to enable image processing of the inhibition diameters one finds on Petri dishes to read out an antibiogram result. Putting such diagnostic tests and the ability to interpret them into the hand of healthcare providers is a key challenge to surmount, and educating patients about the right expectations as to when an antibiotic is not indicated based on such diagnostic tests is another.

While team innovations submitted to the Innovate4Health Design Sprint should not involve piloting an unproven, novel diagnostic test, scaling up already promising or proven approaches also involves innovation. Behavior change interventions can be critical to the adoption of such approaches.

Appropriate diagnostic tools also produce data for surveillance of AMR infections and diseases, allowing decision-makers to establish guidelines and support the rational use of antibiotics. However, inadequate or potentially biased surveillance can lead to a misalignment of actions to reality. For example, if a surveillance network banks on hospitals that are heavy users of antibiotics, and if these hospitals are more likely to be part of a drug company’s surveillance network, then the findings risk being biased towards reporting a higher prevalence of drug resistance than may be found elsewhere in the community. However, moving prematurely to a second-line treatment can be more expensive and lead to less effective stewardship of these second-line antibiotics.

Resources:

• Effects of rapid diagnostic tests on antibiotic prescribing.

• Multi-country cluster-randomized trial on the use of rapid diagnostic tests for malaria.

• Médecins sans Frontières Mini-Lab Project is described further here.

• A description of how the Antibiogo app assists with the reading of microbiology test results can be found here.

Prescribing takes place in both the hospital and the outpatient settings. Managing in-hospital prescription of antibiotics is quite different than in the outpatient setting. Patients hospitalized with infections often may not have responded effectively to oral antibiotics. Parenteral antibiotics may be more expensive second-line antibiotics, require parenteral or intravenous administration, and adjustment in the choice of antibiotics once microbiology culture and sensitivity tests return from the laboratory. Particularly in resource-limited settings, one in 10 patients may acquire healthcare-associated infections while they are undergoing treatment. In low- and middle-income countries, a WHO report notes that over one in ten patients undergoing surgery risk become infected in the process, and in Africa, up to a fifth of women undergoing caesarean section in delivering a baby may suffer from a wound infection. Many of the measures to prevent such infections have been captured in guidelines, such as those provided by the WHO, and in antimicrobial stewardship programs. However, much innovation is still needed to encourage the practice and scale-up the adoption of such measures. This requires behavioral change approaches, with both financial and non-financial incentives, as well as ways to change the education, training, and tools for providers.

Some of the most important points of intervention for antimicrobial stewardship lie in outpatient clinics and management of over-prescription and inappropriate prescription of antibiotics. In the outpatient clinic setting, patients present to healthcare workers with a range of symptoms. Any of a number of symptoms or signs may suggest a bacterial infection treatable with antibiotics—fever, shaking chills, cough, sore throat, abdominal pain, burning on urination, a wound with drainage. Some of these symptoms, however, are non-specific and could well indicate a viral infection, not susceptible to treatment with antibiotics. In outpatient settings in the US, nearly a third of antibiotic prescriptions were determined to be unnecessary.

Some behavior change interventions have addressed such overprescribing in the outpatient setting. For example, in Thailand, patients were offered pharyngeal mirrors to view tonsillar exudate (or its absence) in the treatment of sore throat, thereby empowering patients to ask if they really need antibiotic treatment. Virus treatment kits can help the healthcare provider offer an alternative to antibiotics when not indicated. In Australia, letters to physicians prescribing high volumes of antibiotics in Australia that compared their prescribing rates to peers led to a 9.3-12.3% drop in their antibiotic prescription rates.

Resources:

• Cochrane review of interventions to improve prescribing practices in hospital settings.

• Cochrane review of interventions to improve prescribing practices in outpatient settings.

• Cochrane review on delayed prescribing.

Effective dispensing practices from pharmacies can be undermined by financial incentives (e.g., dispensing fees based on a percentage of a drug’s price as opposed to a flat fee) or substandard antibiotics in the supply chain. Education at the pharmacy/drug-store level can target practices that support the development of AMR, including dispensing antibiotics with expired prescriptions or no prescription at all. These outlets also provide valuable opportunities to intervene to detect substandard and falsified or counterfeit medicines in the supply chain which can undermine the effective treatment of infections, especially when a drug is at an ineffective dose as has been observed in several LMICs.

Resources:

• Systematic review of interventions to improve dispensing practices in low- and middle-income countries.

• Example of issues with antibiotic overprescribing at Accredited Drug Dispensing Outlets in Tanzania.

Even when appropriately prescribed and dispensed for a bacterial infection, the patient may fail to take an adequate course of antibiotics. A multitude of reasons can explain this failure. The patient may feel better and stop taking the full prescribed course of antibiotics. Or the patient may not have the monies to pay for a full course of antibiotics. Addressing these issues of affordability and adherence can support the proper access and follow-through of the use of antibiotics to slow the further spread of AMR. Awareness-raising campaigns to deter patients from taking antibiotics inappropriately, such as for viral infections, have been rolled out around the world. Yet the number of deaths due to inadequate access to antimicrobials is still estimated to be higher than those caused by drug-resistant infections at 5.7 million deaths per year. Work is needed to both change how individuals use and regard antibiotics and to ensure they have the means to access these drugs when they are needed.

Resources:

• WHO global survey on antibiotic awareness campaigns.

• Cochrane review on the effects of providing written material to patients on rates of antibiotic use for upper respiratory tract infections.

Cutting across all of these areas for intervention are interventions that lessen infections overall and thus lower the use of antibiotics. In the outpatient setting, the prevalence of bacterial infections can help drive the need for more treatment, and in turn, more drug-resistant infections. Maintaining community access to essential health and nutrition services is critical for mitigating indirect effects of an epidemic or pandemic. However, health systems struggle to maintain services during these crises, due to both supply- and demand-side challenges. For example, vaccination efforts can both directly reduce the use of antibiotics by decreasing the incidence of bacterial infections, like pneumonia or typhoid, or indirectly do so by reducing viral infections, like rotavirus diarrhea, that may present and be treated inappropriately with antibiotics. Yet amid COVID-19, the World Health Organization, Gavi, the Vaccine Alliance and partner organizations have noted that in over 68 countries, vaccination campaigns that would have reached 80 million children under a year of age have been interrupted.

In response to COVID-19, healthcare systems have rapidly adapted infection prevention and control (IPC) policies to ensure adequate capacity to isolate and treat patients with potential COVID-19 infection. In some cases, this has resulted in relaxing measures that would prevent the spread of drug-resistant organisms, such as screening, isolation in single rooms and antimicrobial stewardship. Ensuring that IPC measures are strong in and out of times of crisis can help to prevent the spread of hospital-acquired bacterial infections including those caused by antibiotic-resistant bacteria.

Strengthening communities’ resilience to prevent outbreaks and quickly and effectively responding to them should they occur is essential to addressing emerging crises while also holding dual benefits for threats like AMR. Interventions to immunize more individuals, encourage personal protective equipment (PPE) use, bolster infection prevention and control practices, or establish community-led surveillance and diagnosis efforts can help to prevent infections of outbreak potential from surfacing and setting back decades of work.

Resources:

• women’s self-help groups in India addressing PPE shortages by sewing masksWHO action framework on the use of vaccines to prevent AMR.

• Review on differences in IPC measures between low- and middle-income countries and high-income countries.

• Article on women’s self-help groups in India addressing PPE shortages by sewing masks