Voice-over: Welcome to Spotlight on Migraine, the Professional Series, a podcast hosted by the Association of Migraine Disorders. In the Professional Series, we dive deeper into migraine-related topics with the help of guests from the medical field. The content of these episodes is intended for medical professionals but may be useful or interesting for patients as well. This episode is brought to you in part by our generous sponsors, Amgen and Novartis.
Join us as Dr. Francine Touzard Romo presents evidence of the overuse of antibiotics for rhinosinusitis and provides guidelines on when they are appropriate and which options should be used in those cases.
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Dr. Francine Touzard Romo: So I’m going to talk a little bit about the antibiotic treatment used for rhinosinusitis. So overall, antibiotics can be lifesaving drugs; however, we know that overuse of antibiotics are associated with one of the most important public health threats, which is antibiotic resistance, in addition to increasing the risk of adverse events and unnecessary costs. 80% of antibiotic use are used in the outpatient setting, so that’s where the money is. And in 2015, in the United States, 269 million antibiotic prescriptions were dispensed from outpatient pharmacies, meaning that four of every five people will receive an antibiotic prescription per year.
And sinusitis was the most common single diagnosis for which an antibiotic was prescribed. So data from the National Ambulatory and Hospital Medicare Survey have shown that rhinosinusitis is the single — lead to most of the antibiotic prescriptions for ambulatory visits, accounting for about 11% of those antibiotic prescriptions. Antibiotics were prescribed in about 85% of acute rhinosinusitis ambulatory visits and 69% with those with chronic rhinosinusitis.
In addition of knowing that antibiotics are overused in rhinosinusitis, in this cohort, for example, we can see from a sample of 184,000 ambulatory visits, again from the same type of survey, 12.6% of those visits resulted in ambulatory prescriptions, and about 506 prescriptions per 1,000 U.S. population annually. And they convened a group of experts that compared those prescriptions to national guidelines, and they were able to convene that only 70% of those prescriptions were actually appropriate and 30% of those prescriptions were actually inappropriate. And among those with acute respiratory conditions, this number is even higher. 50% of those prescriptions are actually inappropriate.
So we’re not just seeing inappropriate use of antibiotics, but also more people are using more broader-spectrum antibiotics to treat rhinosinusitis. In this study from approximately 1,700 sample visits for sinusitis, we see that only first-line therapy — meaning amoxicillin, penicillin, or amoxicillin with clavulanate — was used as first-line therapy in only 50% of the cases. First-line therapy were prescribed more commonly in the pediatric population, though, than in the adult population, and macrolide was the most common non-first-line antibiotic prescribed for sinusitis.
So we’re overprescribing, and additionally, we’re giving antibiotics that are more broad-spectrum than needed, and we’re giving them as well for longer duration. In this cohort, 3.7 million visits at which antibiotics were prescribed for sinusitis, from the 2016 National Disease and Therapeutic Index, we can see that 46% — again, a pretty high number — received non-first-line antibiotics, and most of them were prescribed for 10 days or longer. So the median duration was 10 days, but 70% of those prescriptions were prescribed for 10 days or longer, and even higher rates for those that had a non-azithromycin antibiotic prescribed.
Despite having enough evidence as well in this meta-analysis that included 12 randomized controlled trials, they didn’t show any difference in clinical success when comparing short courses of treatment, 3 to 7 days, compared to 6 to 10 days for acute rhinosinusitis, with definitely fewer adverse events, as expected, in the short-course treatment group.
So what do the guidelines currently recommend for antibiotic treatment for acute rhinosinusitis? And we have currently the ENT guidelines from 2015 and the IDSA, or Infectious Disease Society, guidelines from 2012. So acute rhinosinusitis is actually seldom — I mean, it’s not usually required for treatment of acute rhinosinusitis. It’s mostly recommended for acute bacterial rhinosinusitis, so most of the cases of acute rhinosinusitis are actually viral.
In some cases that we do — our concern for bacterial rhinosinusitis, which are basically those that have symptoms of rhinosinusitis for less than four weeks — that’s why it’s acute — purulent drainage plus nasal obstruction or facial pain or both, but that have symptoms that fail to improve for over 10 days or that are worsening symptoms within those 10 days after initial improvement. And in those patients, you can either decide starting antibiotics right away or have what we call a “watchful waiting,” which is, basically, try to see if in a period of seven days, they do have resolution of symptoms on their own before starting antibiotics. But if they fail to improve, then you can consider starting antibiotics.
Imaging in acute rhinosinusitis is really not necessary unless we’re thinking about complicated, suspected cases, like, for example, patients that have neurological symptoms or proptosis, facial swelling, then is — or the patient’s immunocompromised. Then you would follow up with imaging. But most of the patients with acute rhinosinusitis will not require antibiotics unless you’re suspecting that they do have a bacterial rhinosinusitis.
So what the guidelines recommend is using amoxicillin or amoxicillin plus clavulanate as first-line therapy for 5 to 10 days. And we do favor the use of amoxicillin with clavulanate, particularly in the U.S. Beta-lactamase inhibitors basically adds coverage for ampicillin-resistant Haemophilus influenzae, Moraxella catarrhalis, and here in the U.S., it’s usually about 35 to 40%. High-dose amoxicillin, meaning a 2-gram dosing, can be considered for patients or in areas where penicillin-resistant Strep pneumo is suspected. And routine antimicrobial coverage for Staph aureus, meaning MRSA, even though they’re colonized, in acute rhinosinusitis is not recommended. And then in those patients that have penicillin allergy, the alternative regimens are doxycycline, fluoroquinolones, third-generation cephalosporins plus clindamycin. Macrolides and Bactrim are usually not recommended, giving high rate of resistant Haemophilus influenzae.
And why is the watchful waiting — what is the evidence behind doing watchful waiting? In this meta-analysis, what included 15 randomized controlled trials comparing antibiotic therapy versus placebo or no treatment, where they recruited about 3,000 adults with acute rhinosinusitis symptoms, most of them, without antibiotics, improved within 14 days of treatment. Only 5 to 11 more people per 100 will be cured faster if they receive an antibiotic versus placebo or no treatment. So the number needed to treat, approximately, to show improvement with an antibiotic in one individual will range between 11 to 15; however, the risk is that more people are going to experience side effects.
So in chronic sinusitis, the role of antibiotics is even more controversial. As most of our colleagues — Dr. Mehle had mentioned, the chronic sinusitis is diagnosed, basically, based on the presence of two to four cardinal symptoms — meaning purulent drainage, facial pain or pressure, nasal obstruction, or decreased sense of smell — for 12 or more weeks, plus an objective evidence of sinus inflammation, usually, most commonly, CT of the sinus or direct endoscopic visualization of that inflammation. And the goal of the treatment of chronic sinusitis is to control that inflammatory process, decrease the edema, promote that sinus drainage, and eradicate infection if present.
But chronic rhinosinusitis doesn’t really — it’s not equivalent that there is an infection present. Given of the chronic inflammatory process that is going, yes, there can be decrease of the blood flow in the area and potentially overgrowth of bacteria in the area, particularly anaerobes. But that doesn’t mean that patients with chronic sinusitis are going to improve with antibiotics — just in the cases where they have acute bacterial exacerbations in the process of chronic sinusitis.
So the treatment is really a multi-disciplinary approach: saline irrigations; intranasal steroids with — or systemic steroids, particularly in the cases where sino-polyposis; antibiotic treatment for acute bacterial exacerbations; the management of co-morbidities, as much of our colleagues have mentioned, asthma, allergies, cystic fibrosis, immunodeficiencies; and then consider surgery in the cases that are appropriate.
Again, the data does suggest that when we compare systemic antibiotics in the cases of chronic rhinosinusitis with placebo, only one study — there’s very limited evidence that, really, antibiotics make a difference in chronic rhinositis (sic). There’s one study in patients without polyposis that they were treated with a macrolide, roxithromycin, for 12 weeks versus placebo, and they only saw a modest improvement in disease-specific quality of life, utilizing the SNOT scale, with a macrolide.
In addition, there is a other randomized controlled trial in patients with and without polyposis treated with a macrolide plus other interventions such as saline irrigation and intranasal corticosteroids, compared to placebo, and they didn’t really show any difference in patient-reported severity among both groups.
So what the guidelines recommend in chronic sinusitis is if you are considering that this patient has a bacterial infection on top of their chronic symptoms, then you can include an antibiotic that has anaerobic coverage, and there is increased prevalence for Staph aureus, particularly in those patients that are colonized, and Pseudomonas aeruginosa. Again, we recommend a short course of antibiotics, usually less than three weeks. There have been studies comparing different types of antibiotics in the treatment of chronic sinusitis — including cephalosporins, amoxicillin with clavulanate, and ciprofloxacin — without any difference in outcomes within the three.
And there’s insufficient evidence to recommend long-term macrolides in the use of chronic sinusitis, so talking about three months of therapy. There has been one study where doxycycline potentially improved polyp score symptoms in patients with chronic sinusitis with polyposis when treated at 12 weeks. And then consider a different class of antibiotics if the patient has used antibiotics within the last three months, so if they already used amoxicillin with clavulanate, consider a different alternative. And consider sinus aspirate cultures in those patients to guide therapy.
So why are we overusing antibiotics and overprescribing antibiotics in sinusitis? So a few of the reasons is clinician knowledge gaps and experience managing sinusitis. That leads to diagnostic uncertainty and over-diagnosis of sinusitis. As we were talking about, sinusitis has a broad differential diagnosis, and not necessarily if the patient comes in with facial pain, it is sinusitis. Sometimes, even the guidelines — for example, there’s no clear guidelines of who are the patients that are the best candidates for watchful waiting. And then controversies in treatment, as we discussed in the case of antibiotics and chronic sinusitis.
Also trying to meet the patient expectations — most of the time when patients present to the clinic, they do want an antibiotic prescription, and that’s what they’re expecting, and the physician’s perception of what is going to satisfy the patient in the visit. Prescriber time pressures — so it’s sometimes easier to just prescribe an antibiotic than really do further evaluation or questions. And then availability to follow up and care — in those patients, particularly, that you’re thinking about doing watchful waiting. If you cannot follow up to see if their symptoms improve, obviously, it’s a caveat.
So as an infectious disease specialist, obviously, I’m here to promote antimicrobial stewardship and try to decrease the use of antibiotics in the cases of sinusitis. In 2016, the CDC published the Core Elements for Outpatient Antimicrobial Stewardship, so for those of you that have outpatient practices and in primary care, these are things that you can implement in your practices. So basically, have commitment from the physicians and from the administration as well to strongly encourage the stewardship. Have action for policy and practice. Track those interventions and see if they’re really making an impact in the antibiotic prescribing and report them — and education and expertise.
Some of those interventions could be easy, such as education — not just educate the clinicians, but also educate the patients and the parents of those patients in the pediatric practices. Audit the clinicians and have feedback to those clinicians of their antibiotic prescribing practices. Use rapid diagnostics — for example, rapid strep, PCRs, [inaudible], CRP, RPPs, rapid flus — all those are useful in making decisions in the outpatient practices. And communication training — train your physicians of how to really talk to the patient about not needing an antibiotic and that they’re not upset about it. Electronic decision support and guidelines from your clinics or from the Department of Health. And try to do more watchful — delay prescriptions instead of right away prescribing antibiotics.
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