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Over-prescribed antibiotics cause significant harm – large US analysis

The over-prescription and unnecessary recommendation of antibiotics is not only leading to antibiotic resistance, but also causing significant patient harm, according to a recent study of 51m people – one of the most comprehensive yet to document the impact of antibiotic overuse in clinical practice.

The researchers, at Intermountain Health and Stanford University, found that annually, there are enough outpatient antibiotics prescribed in the United States to cover 80% of the population, and have highlighted the need for more stewardship programmes and tighter guidelines.

Their study, published in the Journal of Internal Medicine, examined 51m patient encounters over a 15-year-period and focused on upper respiratory infections, where antibiotics were known to be over-prescribed 50% of the time.

The researchers found that some of the most dangerous antibiotics were rarely indicated and commonly used, leading to one in 300 of those patients experiencing side effects dire enough to require a follow up doctor's visit – or even hospital admission.

This was one of the few studies large enough to estimate serious, but rare, adverse events such as a potentially deadly diarrhoeal infection, Clostridium difficile. With previous studies showing 34m unnecessary antibiotic prescriptions annually in the US, this translates to real harm for many patients and families.

“These findings underscore that inappropriately giving patients antibiotics is causing real and widespread harm,” said Dr Harris Carmichael, principal investigator of the study and physician at Intermountain Health in Salt Lake City.

“Having these kinds of side effects for one in a few hundred, or even a thousand, patients may not seem like a lot, but when you look at this problem on a population health level, we’re talking about hundreds of thousands of adverse events severe enough that these patients needed additional care from a doctor.”

That means time off work and school for families, unnecessary doctor visits, and risks of serious infections that can last for months or years.

In the retrospective study, the teams from Intermountain and Stanford reviewed insurance claims from the Clinformatics Data Mark Database.

Using data from Medicare Advantage and commercial insurance patients in all 50 states, inpatient and outpatient administrative claims, pharmaceutical claims, and patient demographics for beneficiaries seen between December 2002 and December 2017, they found 50.9m claims for upper respiratory infections, including sinusitis, pharyngitis, laryngitis, bronchitis and the common cold, representing 23m unique patients.

Researchers then identified instances when patients did and did not receive oral antibiotics for an upper respiratory infection, and if those patients were diagnosed with either diarrhoea, candidiasis, Clostridium difficile infection or a mix of these side effects thereafter.

They found that 62.4% of these upper respiratory infection patients filled a prescription for an antibiotic, consistent with prior studies of this population. After their initial visits, 26% of those patients had a follow-up outpatient visit within 14 days.

The odds of a patient being diagnosed with an adverse event increased 30% for those receiving antibiotics. Adverse events after antibiotics were found in as many as one in 300 prescriptions, depending on the antibiotic prescribed, or one in 1 150 prescriptions overall.

"With millions of visits for upper respiratory infections in the US each year, the extent of these severe adverse events is significant," said Carmichael.

Researchers also found that the antibiotic Cefdinir was the fourth most prescribed antibiotic for these patients, despite it rarely being recommended by prescription guidelines as an appropriate treatment for simple upper respiratory infections.

This drug also had the second highest chance of leading to an adverse event. That means that patients are being prescribed a medication that is either not needed at all or unlikely to be the most appropriate medication for their condition and is routinely causing harm, said Carmichael.

He added that the chance of adverse events is possibly much higher, as these results only captured follow-up visits where their adverse event was coded as such for insurance purposes.

That means the results do not include adverse events where physicians didn’t code for that specific side effect, nor for patients who weren’t sick enough to be seen in a doctor’s rooms but may still have had additional and unnecessary time for recovery.

These findings point to the increasingly important need for antibiotic stewardship programmes, so that physicians are following prescribing guidelines and “only prescribe antibiotics when necessary, and then it’s the right antibiotics for the right condition”, Carmichael added.

When Intermountain implemented its own enhanced antibiotic stewardship programmes, which included explaining to patients why they weren’t being prescribed an antibiotic if they asked for it, the health system reduced their overall prescribing rates by more than 15%.

Intermountain Health is a Utah-based not-for-profit healthcare system and the largest healthcare provider in the Intermountain West of the United States.

“Patients don’t get upset when they don’t get antibiotics, as long as we take the time to explain their condition and that we’re treating them in the way that is best for them,” said Carmichael.

Echoing their conclusions was a study published late last year, led by a South African team and comprising scientists from South African Medical Research Council and Swedish FORTE as well as the College of Health Sciences, University of KwaZulu-Natal.

In their findings, which appeared in JAC-Antimicrobial Resistance, the authors found that antibiotics were “frequently prescribed inappropriately by GPs in the private primary healthcare sector”, and highlighted the need for urgent stewardship interventions.

The wrote that in February 2018, 188  141 antibiotics were prescribed for 174  889 patients who consulted GPs in the private sector. Penicillins were the most frequently prescribed, making up 40.7% of all antibiotics prescribed.

Amoxicillin/clavulanic acid was the most common used, making up 28.6% of all antibiotics prescribed, while diseases of the respiratory system generated the highest number of prescriptions, making up 46.1% of all diagnoses, they wrote.

“Of all prescriptions, 8.8% were appropriate, 32.0% were potentially appropriate, 45.4% were inappropriate and 13.8% could not be assessed. Of the appropriately and potentially appropriately prescribed antibiotics, 30.8% were correct antibiotic selections. Of the correctly selected antibiotics for adults, 57.7% had correct doses. Of the antibiotics prescribed with correct doses for adults, 76.7% had correct dosage frequencies and durations of treatment.”

Study 1 details

Clostridium difficile and other adverse events from overprescribed antibiotics for acute upper respiratory infection

Harris Carmichael, Steven Asch, Eran Bendavid.

Published in the Journal of Internal Medicine on 2 December 2022

Abstract

Background
Guidelines widely recommend avoiding antibiotics for many acute upper respiratory infections (aURIs) to avert adverse events in the absence of likely benefit. However, the extent of harm from these antibiotics remains a subject of debate and could inform patient-centred decision-making. Prior estimates finding a number needed to harm (NNH) between 8 and 10 rely on patient-reported adverse events of any severity. In this analysis, we sought to estimate adverse events by only measuring comparatively severe events that require subsequent clinical evaluation.

Methods
We constructed a retrospective cohort, including 51m patient encounters. Using logistic regression models, we determined the adjusted odds ratio (aOR) of clinically detectable adverse events following antibiotic use compared with events among unexposed individuals with aURIs. Our outcomes included candidiasis, diarrhoea, Clostridium difficile infection (CDI), and a composite outcome.

Findings
From our analysis, 62.4% of the population received antibiotics in an aURI encounter. Observed adverse events in the antibiotic-exposed group were 54 279 and 46,936 for diarrhea and candidiasis, respectively, yielding an aOR of 1.24 and 1.61, and an NNH of 3 126 and 1 975. Observed events of CDI in the exposed group were 30,133, and aORs of isolated CDI and combined adverse events were 1.07 and 1.30, resulting in an NNH of 17 695 and 1 150, respectively. Females were more likely to be diagnosed with any adverse event. Overall antibiotics were found to result in 5.7 additional cases of CDI per 100 000 outpatient prescriptions following an upper respiratory tract infection.

Interpretation
Despite higher NNH than previous methods of analysis, we find substantial iatrogenic harm associated with prescribing antibiotics in aURIs.

Study 2 details

Antibiotic prescribing amongst South African general practitioners in private practice: an analysis of a health insurance database 

Mobolaji Eniola Alabi, Sabiha Yusuf Essack

Published in JAC-Antimicrobial Resistance on 5 October 2022

Abstract

Objectives
To investigate the appropriateness of antibiotic prescribing among GPs in the private primary healthcare sector in South Africa.

Methods
An anonymised national database of claims for antibiotic prescriptions was obtained from a large medical insurer. Antibiotic prescriptions were categorised based on International Classification of Diseases (ICD-10) codes as ‘appropriate’, ‘potentially appropriate’ and ‘inappropriate’ using a classification scheme developed by Chua et al. (BMJ 2019; 364: k5092). Further assessments of antibiotic choice, dosage and duration of treatment were carried out to determine the appropriateness of ‘appropriate’ and ‘potentially appropriate’ prescriptions in comparison with treatment guidelines.

Results
In February 2018, 188 141 antibiotics were prescribed for 174 889 patients who consulted GPs in the private sector. Penicillins were the most frequently prescribed antibiotic class, making up 40.7% of all antibiotics prescribed. Amoxicillin/clavulanic acid was the most frequently prescribed antibiotic, making up 28.6% of all antibiotics prescribed. Diseases of the respiratory system generated the highest number of prescriptions, making up 46.1% of all diagnoses. Of all prescriptions, 8.8% were appropriate, 32.0% were potentially appropriate, 45.4% were inappropriate and 13.8% could not be assessed. Of the appropriately and potentially appropriately prescribed antibiotics, 30.8% were correct antibiotic selections. Of the correctly selected antibiotics for adults, 57.7% had correct doses. Of the antibiotics prescribed with correct doses for adults, 76.7% had correct dosage frequencies and durations of treatment.

Conclusions
The study revealed that antibiotics were frequently prescribed inappropriately by GPs in the private primary healthcare sector. There is thus a need to develop stewardship interventions in the sector.

 

Journal of Internal Medicine article – Clostridium difficile and other adverse events from overprescribed antibiotics for acute upper respiratory infection (Open access)

 

JAC-Antimicrobial Resistance article – Antibiotic prescribing amongst South African general practitioners in private practice: an analysis of a health insurance database (Creative Commons Licence)

 

See more from MedicalBrief archives:

 

Beating C. Diff: A new treatment and restricting common antibiotic

 

Updated guidelines for treatment and care of Clostridium difficile

 

Most difficult C. difficile cases becoming more common

 

Rising antibiotic-resistant infections prompt global study with SA hospitals

 

England’s pharmacists allowed to prescribe antibiotics without GP approval

 

 

 

 

 

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