Could long, high dose courses of antibiotics be the answer to common infections or lead to more AMR problems?

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Many women suffer from urinary tract infection (UTI) symptoms for years, but standard tests don't often provide a diagnosis and standard treatments don't help. But recent research into the detection of infections suggest that some tests are out of date and that treatment recommendations could be leading to increased antimicrobial resistance (AMR) problems. 

For most UTIs, the treatment is a three-to-five-day course of antibiotics. Yet research shows that bacterial resistance is actually caused by repeated use of low-dose antibiotics, and it’s been suggested by the researchers that much higher doses over a longer period of time may be warranted.

CKN spoke with Dr. Trent Yarwood, a Cairns-based infectious diseases physician, about the research as well as the role of the Queensland Statewide Antimicrobial Stewardship Program (QSAMSP) that he leads. QSASMP is an initiative of the Queensland Department of Health to ensure that rural and remote hospitals without their own specialist infection staff are able to access antimicrobial stewardship services.

Antimicrobial stewardship (AMS) is about ensuring patients receive the best antibiotics for the treatment of their infections. AMS programs mostly began in large hospitals in the city, where there were higher rates of drug-resistant infections. But infection happens everywhere - in fact, they are more likely to happen in the bush, and we also know that the rates of some resistant organisms are higher in rural areas than in the cities.

People living in regional areas are much more likely to be admitted to hospital with infections than people in the city. Part of this is to do with hospital services, for example, there are far fewer day-surgery and inpatient mental health and other things that are non-infection related. People in the bush tend to present to hospital later than their city cousins, so when they do go to hospital they are often quite unwell. Most of the infections seen are "straightforward", from a city hospital infection specialist's point of view. However, the patients may be sicker, and need to be investigated and managed without the resources we have available to us in the city.

Our program aims to correct some of this imbalance. The QSAMSP program was established in 2016, and although is based in Brisbane, it provides services via telehealth to Queensland's four remote hospital and health services (HHSs) - Torres-Cape, North West, Central West and South West HHS, which make up much of Cape York and the Torres Strait, and western Queensland from the Gulf of Carpentaria to the NSW border. We're really one of the first programs in the world to be delivering a telehealth-based stewardship program across multiple jurisdictions.

Because AMS teams are usually made up of infection specialists, and antibiotic pharmacists who are concentrated in the larger HHSs, our program provides this support via telephone and video conference, ensuring that people in remote Queensland can have the same access to specialist support as people living in the city. We have a phone hotline, where rural clinicians can speak directly to an infectious diseases physician or an antibiotic pharmacist, and we provide advice on diagnosis and treatment of all sorts of infectious (and possibly some non-infectious) problems along the way, as well as selection and dosing of antibiotics. 

We also do weekly telehealth rounds, where we review the antibiotic selection for patients, and talk to rural docs and pharmacists about where to go next. Delivering services by telehealth has its challenges, but the clinicians in our partner health services really appreciate having ready access to specialist services.

The research paper focuses on one of the more common infections people develop during their life, being UTIs, which account for quite a significant amount of antibiotic use, especially in the community. Unfortunately, for such a common infection, they are actually not that straight-forward to diagnose. 

The tests can be negative even if people have an infection, for example if they are already taking antibiotics then bugs don't grow. Alternatively the results can be positive even when they don't have an infection – if other bugs that live around that area falsely contaminate the sample. 

The symptoms of UTIs can be caused by other non-infections as well, for example local irritation from allergies or skin changes that can occur in women after menopause. Non-infection causes of symptoms with a negative test are much more likely to be one of these mimic causes, rather than a mystery infection with a hidden bacterium.

The paper talks about using a much more sensitive sort of test (called deep sequencing) to look for tiny amounts of bacterial DNA. Because this test is so sensitive, it can pick up DNA from bacteria that have been already killed by antibiotics, or by those "along for the ride" contaminating organisms.

Appropriate antibiotic use is important for treating infection. It’s important to note that all antibiotic use, both appropriate and inappropriate, leads to an increase in antibiotic resistance. Of course, inappropriate use contributes to this resistance, but without any benefit to the patient.

We would be especially concerned about the risks of giving patients without infections very long courses of antibiotics where there may not be any benefit, as this would definitely be higher risk for creating resistance. As the paper identifies, there isn't a reference or "gold standard" test we can use to say that the infection is really present or not, so just as we can't be sure we're not missing infections now, we can't be sure this new test isn't over-calling infections that aren't real.

We have already seen urinary tract infections in Australia which aren't able to be treated with tablet antibiotics - which means people need to be admitted to hospital or given intravenous antibiotics via “hospital in the home” programs. Hospitals and community healthcare staff have become a lot more aware of the dangers of antibiotic resistance over the last few years, and Australia has taken strong action by making AMS programs a mandatory part of hospital accreditation.

There's still a long way to go, though, particularly in the community where patients may not be as aware of the risks of resistance, and healthcare staff may think it's mainly a problem in-hospital. The new national AMR strategy will be released later this year, and it would be great to see more activities engaging the public and building awareness.

Although our QSAMSP is a specialist service, it's really important to highlight that antimicrobial stewardship is everyone's business - other hospital doctors, GPs, as well as patients and the public. Drug resistance isn't going away, and since it's one of the wicked problems - it's often likened to climate change - we need to all contribute. It's really no good saying "oh, but someone else is doing that", because making every prescription the best it can be is important for everyone.

Dr. Trent Yarwood
Director, Queensland Statewide Antimicrobial Stewardship Program
Staff Specialist Infectious Diseases Physician