Pamela R. Hughes, MD

ILLUSTRATIVE CASE

A 64-year-old overweight White man with a history of hypertension, hyperlipidemia, and HF with an ejection fraction (EF) of 40% presents for primary care follow-up after a recent inpatient admission for worsened HF symptoms. At baseline, he is comfortable at rest but becomes dyspneic upon walking to another room within his home. He is already taking a mineralocorticoid receptor antagonist, a high-intensity statin, a beta-blocker, and an angiotensin-converting enzyme (ACE) inhibitor. What other medication should be considered to minimize his cardiovascular (CV)risk?

An estimated 1% to 2% of the world’s adult population has HF.² Although the exact prevalence is difficult to quantify due to variations in definitions and diagnostic methods, the American Heart Association (AHA) estimated that 6.2 million Americans had HF between 2013 and 2016.³ Prevalence increases with age, with an annual incidence of approximately 35 per 1000 by age 85.⁴ Due to the significant morbidity and mortality associated with HF, advancements in treatment are needed.

SGLT2 inhibitors work within the proximal tubule of the kidneys, resulting in increased glucose and sodium excretion with secondary osmotic diuresis and therefore a modest reduction in serum glucose.^1,2,5,6 SGLT2 inhibitors are classically prescribed for hyperglycemia treatment in type 2 diabetes. However, preliminary data suggest that this class of medication also positively impacts cardiac function. The diuresis and natriuresis effects of SGLT2 inhibitors appear to optimize cardiac output and subsequent oxygen consumption through a reduction of afterload and preload.^1,2,5,6 Further, SGLT2 inhibitors may decrease inflammatory pathways and lead to a secondary reduction of cardiac remodeling via a reduction and modulation of inflammatory pathways. This reduction and modulation may also be associated with a reduction in development, and possibly a reversal, of hypertrophic cardiomyopathy, cardiac fibrosis, and atherosclerosis.^5,6 Some of the previously reported adverse effects of SGLT2 inhibitors include urinary tract infection, acute kidney injury, lower extremity amputation, bone fracture, and diabetic ketoacidosis.²

In several studies of patients with type 2 diabetes, SGLT2 inhibitors have shown benefit in reducing CV disease–related death and hospitalization for HF.^1,2,5,6 A recent expert consensus from the American College of Cardiology (ACC) states that SGLT2 therapy should be considered for any patient with type 2 diabetes who also has established atherosclerotic CV disease, HF (a clinical syndrome as defined in ACC/AHA guidelines), or diabetic kidney disease, or who is at a high risk for atherosclerotic CV disease (ie, has signs of end-organ damage, such as left ventricular hypertrophy or retinopathy, or multiple risk factors such as advanced age, smoking, hypertension, and family history).^7,8

Dapagliflozin demonstrated decreased HF exacerbations and CV deaths, improved patient-reported HF symptoms, and lower allcause mortality in patients both with and without diabetes.

Additionally, a 2019 randomized controlled trial (RCT) by Nassif et al showed that, compared to placebo, dapagliflozin significantly improved both patient-reported HF symptoms and cardiac natriuretic peptide levels over 12 weeks in patients with and without diabetes.⁹ In September 2020, ­UpToDate added SGLT2 inhibitors as an option for patients with continued symptoms of HF despite use of appropriate primary agents and mineralocorticoid receptor antagonists, whether or not they have type 2 diabetes; this update was based on 2 studies, 1 of which is reviewed here.¹⁰

STUDY SUMMARY

Dapagliflozin demonstrated better CV outcomes than placebo

The Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) study is an RCT that compared dapagliflozin to placebo among 4744 patients ages 18 years and older who had HF with an EF ≤ 40% and NYHA class II, III, or IV symptoms. The study included patients with (41.8%) and without diabetes. Most patients were male (76.2%-77%), White (70%), and European (44.7%-46.1%).

Patients were randomized to receive either dapagliflozin 10 mg/d or a matching placebo in addition to standard HF therapy (including an ACE inhibitor, angiotensin receptor blocker, or sacubitril-valsartan plus a beta-blocker unless contraindicated; mineralocorticoid antagonist use was encouraged). Follow-up occurred at 14 days, 60 days, 4 months, and then every 4 months, for an average of about 18 months. Patients with diabetes continued to use their glucose-lowering therapies, with dose adjustments, as needed.

Continue to: The primary outcome...

The primary outcome was a composite of worsening HF (hospitalization or urgent visit requiring intravenous HF therapy) or death from a CV cause. Secondary outcomes included a composite of hospitalization for HF or CV death; total number of hospitalizations for HF (including repeat admissions) and CV death; a change in Kansas City Cardiomyopathy Questionnaire symptom score; a composite of worsening renal function including a sustained (≥ 28 d) decline in the estimated glomerular filtration rate (eGFR) of ≥ 50%, end-stage renal disease (defined as sustained eGFR of < 15 mL/min/1.73 m², sustained dialysis, or renal transplantation), or renal death; and death from any cause.

The primary outcome of worsening HF or death from CV causes occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio [HR] = 0.74; 95% CI, 0.65-0.85; P < .001). The composite score of hospitalizations for HF plus death from a CV cause was lower in the dapagliflozin group compared to the placebo group (HR = 0.75; 95% CI, 0.65-0.85; P < .001).

Integration of SGLT2 inhibitors into a patient’s medication regimen may require dose adjustments of other medications.

A total of 276 patients (11.6%) in the dapagliflozin group and 329 patients (13.9%) in the placebo group died from any cause (HR = 0.83; 95% CI, 0.71-0.97). More patients in the dapagliflozin group than in the placebo group had an improvement in symptom score (58.3% vs 50.9%; odds ratio = 1.15; 95% CI, 1.08-1.23; P < .001). Renal composite outcome did not differ between the 2 treatment groups. Potential adverse effects included volume depletion, renal adverse event, and major hypoglycemia, which occurred at the same rate in the treatment and placebo groups. There was no difference in outcomes or adverse effects between patients with and without diabetes.¹

WHAT'S NEW

Evidence supports dapagliflozin use in a new patient population

The DAPA-HF study compared dapagliflozin to placebo in HF patients both with and without diabetes and demonstrated decreased HF exacerbations and CV deaths, improved ­patient-reported HF symptoms, and lower all-cause mortality in the treatment group. This study supports use of dapagliflozin in a new patient population—those with HF—rather than solely in patients with diabetes, as the drug was originally marketed.

CAVEATS

Specific study population may limit generalizability

The DAPA-HF study included mostly male, White, European patients followed for an average of 18.2 months as part of initial Phase III studies funded by AstraZeneca (the pharmaceutical company that developed dapagliflozin). Given the potential conflict due to funding, all statistical results were verified by an independent academic group, and analyses were completed with an intention-to-treat model. The outlined benefits described here were only studied in a population of patients with reduced EF (≤ 40%), so the impact remains unclear for patients with preserved EF. Safety and benefits beyond 24 months were not studied in this RCT; therefore long-term data are still unknown.

Continue to: CHALLENGES TO IMPLEMENTATION

Adding an SGLT2 inhibitor may be cost prohibitive for some patients

An SGLT2 inhibitor costs, on average, $500 to $600 for a 30-day supply, which may be prohibitive for some patients.¹¹ Integration of SGLT2 inhibitors into a patient’s medication regimen may require dose adjustments of other medications, particularly glucose-lowering therapies, and the optimal prioritization of medications is not yet known.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 64-year-old overweight White man with a history of hypertension, hyperlipidemia, and HF with an ejection fraction (EF) of 40% presents for primary care follow-up after a recent inpatient admission for worsened HF symptoms. At baseline, he is comfortable at rest but becomes dyspneic upon walking to another room within his home. He is already taking a mineralocorticoid receptor antagonist, a high-intensity statin, a beta-blocker, and an angiotensin-converting enzyme (ACE) inhibitor. What other medication should be considered to minimize his cardiovascular (CV)risk?

An estimated 1% to 2% of the world’s adult population has HF.² Although the exact prevalence is difficult to quantify due to variations in definitions and diagnostic methods, the American Heart Association (AHA) estimated that 6.2 million Americans had HF between 2013 and 2016.³ Prevalence increases with age, with an annual incidence of approximately 35 per 1000 by age 85.⁴ Due to the significant morbidity and mortality associated with HF, advancements in treatment are needed.

SGLT2 inhibitors work within the proximal tubule of the kidneys, resulting in increased glucose and sodium excretion with secondary osmotic diuresis and therefore a modest reduction in serum glucose.^1,2,5,6 SGLT2 inhibitors are classically prescribed for hyperglycemia treatment in type 2 diabetes. However, preliminary data suggest that this class of medication also positively impacts cardiac function. The diuresis and natriuresis effects of SGLT2 inhibitors appear to optimize cardiac output and subsequent oxygen consumption through a reduction of afterload and preload.^1,2,5,6 Further, SGLT2 inhibitors may decrease inflammatory pathways and lead to a secondary reduction of cardiac remodeling via a reduction and modulation of inflammatory pathways. This reduction and modulation may also be associated with a reduction in development, and possibly a reversal, of hypertrophic cardiomyopathy, cardiac fibrosis, and atherosclerosis.^5,6 Some of the previously reported adverse effects of SGLT2 inhibitors include urinary tract infection, acute kidney injury, lower extremity amputation, bone fracture, and diabetic ketoacidosis.²

In several studies of patients with type 2 diabetes, SGLT2 inhibitors have shown benefit in reducing CV disease–related death and hospitalization for HF.^1,2,5,6 A recent expert consensus from the American College of Cardiology (ACC) states that SGLT2 therapy should be considered for any patient with type 2 diabetes who also has established atherosclerotic CV disease, HF (a clinical syndrome as defined in ACC/AHA guidelines), or diabetic kidney disease, or who is at a high risk for atherosclerotic CV disease (ie, has signs of end-organ damage, such as left ventricular hypertrophy or retinopathy, or multiple risk factors such as advanced age, smoking, hypertension, and family history).^7,8

Dapagliflozin demonstrated decreased HF exacerbations and CV deaths, improved patient-reported HF symptoms, and lower allcause mortality in patients both with and without diabetes.

Additionally, a 2019 randomized controlled trial (RCT) by Nassif et al showed that, compared to placebo, dapagliflozin significantly improved both patient-reported HF symptoms and cardiac natriuretic peptide levels over 12 weeks in patients with and without diabetes.⁹ In September 2020, ­UpToDate added SGLT2 inhibitors as an option for patients with continued symptoms of HF despite use of appropriate primary agents and mineralocorticoid receptor antagonists, whether or not they have type 2 diabetes; this update was based on 2 studies, 1 of which is reviewed here.¹⁰

STUDY SUMMARY

Dapagliflozin demonstrated better CV outcomes than placebo

The Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) study is an RCT that compared dapagliflozin to placebo among 4744 patients ages 18 years and older who had HF with an EF ≤ 40% and NYHA class II, III, or IV symptoms. The study included patients with (41.8%) and without diabetes. Most patients were male (76.2%-77%), White (70%), and European (44.7%-46.1%).

Patients were randomized to receive either dapagliflozin 10 mg/d or a matching placebo in addition to standard HF therapy (including an ACE inhibitor, angiotensin receptor blocker, or sacubitril-valsartan plus a beta-blocker unless contraindicated; mineralocorticoid antagonist use was encouraged). Follow-up occurred at 14 days, 60 days, 4 months, and then every 4 months, for an average of about 18 months. Patients with diabetes continued to use their glucose-lowering therapies, with dose adjustments, as needed.

Continue to: The primary outcome...

The primary outcome was a composite of worsening HF (hospitalization or urgent visit requiring intravenous HF therapy) or death from a CV cause. Secondary outcomes included a composite of hospitalization for HF or CV death; total number of hospitalizations for HF (including repeat admissions) and CV death; a change in Kansas City Cardiomyopathy Questionnaire symptom score; a composite of worsening renal function including a sustained (≥ 28 d) decline in the estimated glomerular filtration rate (eGFR) of ≥ 50%, end-stage renal disease (defined as sustained eGFR of < 15 mL/min/1.73 m², sustained dialysis, or renal transplantation), or renal death; and death from any cause.

The primary outcome of worsening HF or death from CV causes occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio [HR] = 0.74; 95% CI, 0.65-0.85; P < .001). The composite score of hospitalizations for HF plus death from a CV cause was lower in the dapagliflozin group compared to the placebo group (HR = 0.75; 95% CI, 0.65-0.85; P < .001).

Integration of SGLT2 inhibitors into a patient’s medication regimen may require dose adjustments of other medications.

A total of 276 patients (11.6%) in the dapagliflozin group and 329 patients (13.9%) in the placebo group died from any cause (HR = 0.83; 95% CI, 0.71-0.97). More patients in the dapagliflozin group than in the placebo group had an improvement in symptom score (58.3% vs 50.9%; odds ratio = 1.15; 95% CI, 1.08-1.23; P < .001). Renal composite outcome did not differ between the 2 treatment groups. Potential adverse effects included volume depletion, renal adverse event, and major hypoglycemia, which occurred at the same rate in the treatment and placebo groups. There was no difference in outcomes or adverse effects between patients with and without diabetes.¹

WHAT'S NEW

Evidence supports dapagliflozin use in a new patient population

The DAPA-HF study compared dapagliflozin to placebo in HF patients both with and without diabetes and demonstrated decreased HF exacerbations and CV deaths, improved ­patient-reported HF symptoms, and lower all-cause mortality in the treatment group. This study supports use of dapagliflozin in a new patient population—those with HF—rather than solely in patients with diabetes, as the drug was originally marketed.

CAVEATS

Specific study population may limit generalizability

The DAPA-HF study included mostly male, White, European patients followed for an average of 18.2 months as part of initial Phase III studies funded by AstraZeneca (the pharmaceutical company that developed dapagliflozin). Given the potential conflict due to funding, all statistical results were verified by an independent academic group, and analyses were completed with an intention-to-treat model. The outlined benefits described here were only studied in a population of patients with reduced EF (≤ 40%), so the impact remains unclear for patients with preserved EF. Safety and benefits beyond 24 months were not studied in this RCT; therefore long-term data are still unknown.

Continue to: CHALLENGES TO IMPLEMENTATION

Adding an SGLT2 inhibitor may be cost prohibitive for some patients

An SGLT2 inhibitor costs, on average, $500 to $600 for a 30-day supply, which may be prohibitive for some patients.¹¹ Integration of SGLT2 inhibitors into a patient’s medication regimen may require dose adjustments of other medications, particularly glucose-lowering therapies, and the optimal prioritization of medications is not yet known.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 64-year-old overweight White man with a history of hypertension, hyperlipidemia, and HF with an ejection fraction (EF) of 40% presents for primary care follow-up after a recent inpatient admission for worsened HF symptoms. At baseline, he is comfortable at rest but becomes dyspneic upon walking to another room within his home. He is already taking a mineralocorticoid receptor antagonist, a high-intensity statin, a beta-blocker, and an angiotensin-converting enzyme (ACE) inhibitor. What other medication should be considered to minimize his cardiovascular (CV)risk?

An estimated 1% to 2% of the world’s adult population has HF.² Although the exact prevalence is difficult to quantify due to variations in definitions and diagnostic methods, the American Heart Association (AHA) estimated that 6.2 million Americans had HF between 2013 and 2016.³ Prevalence increases with age, with an annual incidence of approximately 35 per 1000 by age 85.⁴ Due to the significant morbidity and mortality associated with HF, advancements in treatment are needed.

SGLT2 inhibitors work within the proximal tubule of the kidneys, resulting in increased glucose and sodium excretion with secondary osmotic diuresis and therefore a modest reduction in serum glucose.^1,2,5,6 SGLT2 inhibitors are classically prescribed for hyperglycemia treatment in type 2 diabetes. However, preliminary data suggest that this class of medication also positively impacts cardiac function. The diuresis and natriuresis effects of SGLT2 inhibitors appear to optimize cardiac output and subsequent oxygen consumption through a reduction of afterload and preload.^1,2,5,6 Further, SGLT2 inhibitors may decrease inflammatory pathways and lead to a secondary reduction of cardiac remodeling via a reduction and modulation of inflammatory pathways. This reduction and modulation may also be associated with a reduction in development, and possibly a reversal, of hypertrophic cardiomyopathy, cardiac fibrosis, and atherosclerosis.^5,6 Some of the previously reported adverse effects of SGLT2 inhibitors include urinary tract infection, acute kidney injury, lower extremity amputation, bone fracture, and diabetic ketoacidosis.²

In several studies of patients with type 2 diabetes, SGLT2 inhibitors have shown benefit in reducing CV disease–related death and hospitalization for HF.^1,2,5,6 A recent expert consensus from the American College of Cardiology (ACC) states that SGLT2 therapy should be considered for any patient with type 2 diabetes who also has established atherosclerotic CV disease, HF (a clinical syndrome as defined in ACC/AHA guidelines), or diabetic kidney disease, or who is at a high risk for atherosclerotic CV disease (ie, has signs of end-organ damage, such as left ventricular hypertrophy or retinopathy, or multiple risk factors such as advanced age, smoking, hypertension, and family history).^7,8

Dapagliflozin demonstrated decreased HF exacerbations and CV deaths, improved patient-reported HF symptoms, and lower allcause mortality in patients both with and without diabetes.

Additionally, a 2019 randomized controlled trial (RCT) by Nassif et al showed that, compared to placebo, dapagliflozin significantly improved both patient-reported HF symptoms and cardiac natriuretic peptide levels over 12 weeks in patients with and without diabetes.⁹ In September 2020, ­UpToDate added SGLT2 inhibitors as an option for patients with continued symptoms of HF despite use of appropriate primary agents and mineralocorticoid receptor antagonists, whether or not they have type 2 diabetes; this update was based on 2 studies, 1 of which is reviewed here.¹⁰

STUDY SUMMARY

Dapagliflozin demonstrated better CV outcomes than placebo

The Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) study is an RCT that compared dapagliflozin to placebo among 4744 patients ages 18 years and older who had HF with an EF ≤ 40% and NYHA class II, III, or IV symptoms. The study included patients with (41.8%) and without diabetes. Most patients were male (76.2%-77%), White (70%), and European (44.7%-46.1%).

Patients were randomized to receive either dapagliflozin 10 mg/d or a matching placebo in addition to standard HF therapy (including an ACE inhibitor, angiotensin receptor blocker, or sacubitril-valsartan plus a beta-blocker unless contraindicated; mineralocorticoid antagonist use was encouraged). Follow-up occurred at 14 days, 60 days, 4 months, and then every 4 months, for an average of about 18 months. Patients with diabetes continued to use their glucose-lowering therapies, with dose adjustments, as needed.

Continue to: The primary outcome...

The primary outcome was a composite of worsening HF (hospitalization or urgent visit requiring intravenous HF therapy) or death from a CV cause. Secondary outcomes included a composite of hospitalization for HF or CV death; total number of hospitalizations for HF (including repeat admissions) and CV death; a change in Kansas City Cardiomyopathy Questionnaire symptom score; a composite of worsening renal function including a sustained (≥ 28 d) decline in the estimated glomerular filtration rate (eGFR) of ≥ 50%, end-stage renal disease (defined as sustained eGFR of < 15 mL/min/1.73 m², sustained dialysis, or renal transplantation), or renal death; and death from any cause.

The primary outcome of worsening HF or death from CV causes occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio [HR] = 0.74; 95% CI, 0.65-0.85; P < .001). The composite score of hospitalizations for HF plus death from a CV cause was lower in the dapagliflozin group compared to the placebo group (HR = 0.75; 95% CI, 0.65-0.85; P < .001).

Integration of SGLT2 inhibitors into a patient’s medication regimen may require dose adjustments of other medications.

A total of 276 patients (11.6%) in the dapagliflozin group and 329 patients (13.9%) in the placebo group died from any cause (HR = 0.83; 95% CI, 0.71-0.97). More patients in the dapagliflozin group than in the placebo group had an improvement in symptom score (58.3% vs 50.9%; odds ratio = 1.15; 95% CI, 1.08-1.23; P < .001). Renal composite outcome did not differ between the 2 treatment groups. Potential adverse effects included volume depletion, renal adverse event, and major hypoglycemia, which occurred at the same rate in the treatment and placebo groups. There was no difference in outcomes or adverse effects between patients with and without diabetes.¹

WHAT'S NEW

Evidence supports dapagliflozin use in a new patient population

The DAPA-HF study compared dapagliflozin to placebo in HF patients both with and without diabetes and demonstrated decreased HF exacerbations and CV deaths, improved ­patient-reported HF symptoms, and lower all-cause mortality in the treatment group. This study supports use of dapagliflozin in a new patient population—those with HF—rather than solely in patients with diabetes, as the drug was originally marketed.

CAVEATS

Specific study population may limit generalizability

The DAPA-HF study included mostly male, White, European patients followed for an average of 18.2 months as part of initial Phase III studies funded by AstraZeneca (the pharmaceutical company that developed dapagliflozin). Given the potential conflict due to funding, all statistical results were verified by an independent academic group, and analyses were completed with an intention-to-treat model. The outlined benefits described here were only studied in a population of patients with reduced EF (≤ 40%), so the impact remains unclear for patients with preserved EF. Safety and benefits beyond 24 months were not studied in this RCT; therefore long-term data are still unknown.

Continue to: CHALLENGES TO IMPLEMENTATION

Adding an SGLT2 inhibitor may be cost prohibitive for some patients

An SGLT2 inhibitor costs, on average, $500 to $600 for a 30-day supply, which may be prohibitive for some patients.¹¹ Integration of SGLT2 inhibitors into a patient’s medication regimen may require dose adjustments of other medications, particularly glucose-lowering therapies, and the optimal prioritization of medications is not yet known.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

An estimated 30 million cases of acute rhinosinusitis (ARS) occur every year in the United States.¹ More than 80% of people with ARS are prescribed antibiotics in North America, accounting for 15% to 20% of all antibiotic prescriptions in the adult outpatient setting.^2,3 Many of these prescriptions are unnecessary, as the most common cause of ARS is a virus.^4,5 Evidence consistently shows that symptoms of ARS will resolve spontaneously in most patients and that only those patients with severe or prolonged symptoms require consideration of antibiotic therapy.^1,2,4,6 Nearly half of all patients will improve within 1 week and two-thirds of patients will improve within 2 weeks without the use of antibiotics.⁷ In children, only about 6% to 7% presenting with upper respiratory symptoms meet the criteria for acute bacterial rhinosinusitis (ABRS),⁸ which we’ll detail in a bit. For most patients, treatment should consist of symptom management.⁵

But what about the minority who require antibiotic therapy? This article reviews how to evaluate patients with ARS, identify those who require antibiotics, and prescribe the most appropriate antibiotic treatment regimens.

Diagnosis: Distinguishing viral from bacterial disease

ARS is defined as the sudden onset of purulent nasal discharge plus either nasal blockage or facial pressure/pain lasting < 4 weeks.^3,9 Additional signs and symptoms may include postnasal drip, a reduced sense of smell, sinus tenderness to palpation, and maxillary toothaches.^10,11

ARS may be viral or bacterial in etiology, with the most common bacterial organisms being Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.^1,3,5 The most common viral causes are influenza, parainfluenza, and rhinovirus. Approximately 90% to 98% of cases of ARS are viral^6,11; only about 0.5% to 2% of viral rhinosinusitis episodes are complicated by bacterial infection.^1,10-12

Diagnose ABRS when symptoms of ARS fail to improve after 10 days or symptoms of ARS worsen within 10 days after initial improvement (“double sickening”).^1,11 Symptoms that are significantly associated with ABRS are unilateral sinus pain and reported maxillary pain. The presence of facial or dental pain correlates with ABRS but does not identify the specific sinus involved.¹

Approximately 90% to 98% of cases of acute rhinosinusitis are viral; only about 0.5% to 2% of viral rhinosinusitis episodes are complicated by bacterial infection.

There isn’t good correlation between patients saying they have sinusitis and actually having it.¹³ A 2019 meta-analysis by Ebell et al¹⁴ reported that based on limited data, the overall clinical impression, fetid odor on the breath, and pain in the teeth are the best individual clinical predictors of ABRS.

As recommended by the Infectious Disease Society of America (IDSA), a diagnosis of ABRS is also reasonable in patients who present with severe symptoms at the onset.⁶ Although there is no consensus about what constitutes “severe symptoms,” they are often described as a temperature ≥ 102°F (39°C) plus 3 to 4 days of purulent nasal drainage.^1,4,6

Continue to: Additional symptoms of ABRS may include...

Additional symptoms of ABRS may include cough, fatigue, decreased or lack of sense of smell (hyposmia or anosmia), and ear pressure.¹⁰ Another sign of “double sickening” is the development of a fever after several days of symptoms.^1,9,15 Viral sinusitis typically lasts 5 to 7 days with a peak at days 2 to 3.^1,15 If symptoms continue for 10 days, there is a 60% chance of bacterial sinusitis, although some viral rhinosinusitis symptoms persist for > 14 days.^1,5 Beyond 4 to 12 weeks, sinusitis is classified as subacute or chronic.³

Physical exam findings and the limited roles of imaging and labs

Common physical exam findings associated with the diagnosis of ABRS include altered speech indicating nasal obstruction; edema or erythema of the skin indicating congested capillaries; tenderness to palpation over the cheeks or upper teeth; odorous breath; and purulent drainage from the nose or in the posterior pharynx.

In a study by Hansen et al¹³ (N = 174), the only sign that showed significant association with ABRS (diagnosed by sinus aspiration or lavage) was unilateral tenderness of the maxillary sinuses. The presence of purulent drainage in the nose or posterior pharynx also has significant diagnostic value, as it predicts the presence of bacteria on antral aspiration.¹ Purulent discharge in the pharynx is associated with a higher likelihood of benefit from antibiotic therapy compared to placebo (number needed to treat [NNT] = 8).¹⁶ However, colored nasal discharge indicates the presence of neutrophils—not bacteria—and does not predict the likelihood of bacterial sinus infection.^14,17 Therefore, the history and physical exam should focus on location of pain (sinus and/or teeth), duration of symptoms, presence of fever, change in symptom severity, attempted home therapies, sinus tenderness on exam, breath odor, and purulent drainage seen in the nasal cavity or posterior pharynx.^13,14

Radiographic imaging has no role in the diagnosis or treatment of uncomplicated ABRS because viral and bacterial etiologies have similar radiographic appearances. Additionally, employing radiologic imaging would increase health care costs by at least 4-fold.^5,6,8,17 The American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) clinical practice guidelines recommend against radiographic imaging for patients who meet the diagnostic criteria for ABRS unless concern exists for a complication or an alternate diagnosis is suspected.¹ Computed tomography (CT) imaging of the sinuses may be warranted in patients with severe headaches, facial swelling, cranial nerve palsies, or bulging of the eye (proptosis), all of which indicate a potential complication of ABRS.¹

Laboratory evaluations. ABRS is a clinical diagnosis; therefore, routine lab work, such as a white blood cell count, C-­reactive protein (CRP) level, and/or erythrocyte sedimentation rate (ESR), are not indicated unless an alternate diagnosis is suspected.^1,5,13,18,19

Continue to: In one study...

In one study, CRP > 10 mg/L and ESR > 10 mm/h were the strongest individual predictors of purulent antral puncture aspirate or positive bacterial culture of aspirate, which is considered diagnostic for ABRS. ²⁰ However, CRP and ESR by themselves are not adequate to diagnose ABRS.²⁰ This study developed a clinical decision rule that used symptoms, signs, and laboratory values to rate the likelihood of ABRS as being either low, moderate, or high. However, this clinical decision rule has not been prospectively validated.

Thus, CRP and ESR elevations can support the diagnosis of ABRS, but the low sensitivity of these tests precludes their use as a screening tool for ABRS.^14,18 Studies by Ebell¹⁹ and Huang²¹ have shown some benefit to dipstick assay of nasal secretions for the diagnosis of ABRS, but this method is not validated or widely used.^19,21

Treatment: From managing symptoms to prescribing antibiotics

Overprescribing antibiotics for ARS is a prominent health care issue. In fact, 5 of 9 placebo-controlled studies showed that most people improve within 2 weeks regardless of antibiotic use (N = 1058).³ Therefore, weigh the decision to treat ABRS with antibiotics against the risk for potential adverse reactions and within the context of antibiotic stewardship.^2,9,12,22-24 Consider antibiotics only if patients meet the diagnostic criteria for ABRS (TABLE 1^1,6) or, occasionally, for patients with severe symptoms upon presentation, such as a temperature ≥ 102°F (39°C) plus purulent nasal discharge for 3 to 4 days.¹ The most commonly reported adverse effects of antibiotics are gastrointestinal in nature and include nausea, vomiting, and diarrhea.^2,9

Symptomatic management for both ARS and ABRS is recommended as first-line therapy; it should be offered to patients before making a diagnosis of ABRS.^1,5,9,25 Consider using analgesics, topical intranasal steroids, and/or nasal saline irrigation to alleviate symptoms and improve quality of life.^1,5,25 Interventions with questionable or unproven efficacy include the use of antihistamines, systemic steroids, decongestants, and mucolytics, but they may be considered on an individual basis.¹ A systematic review found that topical nasal steroids relieved facial pain and nasal congestion in patients with rhinitis and acute sinusitis (NNT = 14).^1,26

Even after diagnosing ABRS, clinicians should offer watchful waiting and symptomatic therapies as long as patients have adequate access to follow-up (TABLE 2,^1,15FIGURE^1,6). Antibiotic therapy can then be initiated if symptoms do not improve after an additional 7 days of watchful waiting or if symptoms worsen at any time. It is reasonable to give patients a prescription to keep on hand to be used if symptoms worsen, with instructions to notify the provider if antibiotics are started.¹

Continue to: Antibiotic therapy

Antibiotic therapy. The rationale for treating ABRS with antibiotics is to expedite recovery and prevent complications such as periorbital or orbital cellulitis, meningitis, frontal osteomyelitis, cavernous sinus thrombosis, and other serious illness.²⁷ Antibiotic treatment is associated with a shorter duration of symptoms (NNT = 19) but an increased risk of adverse events (NNH = 8).^7,19

Diagnose acute bacterial rhinosinusitis when symptoms of acute rhinosinusitis fail to improve after 10 days or symptoms of ARS worsen within 10 days after initial improvement.

Amoxicillin with or without clavulanate for 5 to 10 days is first-line antibiotic therapy for most adults with ABRS.^1,3,5,8,9,11 Per ­AAO-HNS, the “justification for amoxicillin as first-line treatment relates to its safety, efficacy, low cost, and narrow microbiologic spectrum.”¹ Amoxicillin may be dosed 500 mg tid for 5 to 10 days. Amoxicillin/clavulanate (Augmentin) is recommended for patients with comorbid conditions or with increased risk of bacterial resistance. Dosing for amoxicillin/clavulanate is 500/125 mg tid or 875/125 mg bid for 5 to 10 days. Duration of therapy should be determined by the severity of symptoms.⁵

For penicillin-allergic patients, doxycycline or a respiratory fluoroquinolone (levofloxacin or moxifloxacin) is considered first-line treatment.^1,6 Doxycycline is preferred because of its narrower spectrum and fewer adverse effects than the fluoroquinolones. Fluoroquinolones should be reserved for patients who fail first-line treatment and are penicillin allergic.¹ Because of the high rates of resistance among S pneumoniae and H influenzae, macrolides, trimethoprim/sulfamethoxazole (TMP/SMX), and cephalosporins are not recommended as first-line therapy.^1,5

How antibiotic options compare. A Cochrane review of 54 studies comparing different antibiotics showed no antibiotic was superior.³ Of the 54 studies, 6 studies (N = 1887) were pooled to compare cephalosporins to amoxicillin/clavulanate at 7 to 15 days. The findings indicated a statistically significant difference for amoxicillin/clavulanate with a relative risk (RR) of 1.37 (confidence interval [CI], 1.04-1.8).³ However, none of these 6 studies were graded as having a low risk of bias; therefore, confidence in this finding was deemed limited due to the quality of included studies. The failure rate for cephalosporins was 12% vs 8% for amoxicillin/clavulanate.³

Colored nasal discharge indicates the presence of neutrophils—not bacteria—and does not predict the likelihood of bacterial sinus infection.

Treatment failure is considered when a patient has not improved by Day 7 after ABRS diagnosis (with or without medication) or when symptoms worsen at any time. If watchful waiting was chosen and a safety net prescription was provided, the antibiotics should be filled and started. If no antibiotic was prescribed at the time watchful waiting commenced, the patient should return for further evaluation and be started on antibiotics. If antibiotics were prescribed initially for severe symptoms, a change in antibiotic therapy is indicated, and a broader-spectrum antibiotic should be chosen. If amoxicillin was prescribed, the patient should be switched to amoxicillin/clavulanate, doxycycline, a respiratory fluoroquinolone, or a combination of clindamycin plus a third-generation cephalosporin.¹

Continue to: Diagnosis and management of pediatric patients

Diagnosis and management of pediatric patients

Diagnosis of ABRS in children is defined as an acute upper respiratory infection (URI) accompanied by persistent nasal discharge, daytime cough for ≥ 10 days without improvement, an episode of “double sickening,” or severe onset with a temperature ≥ 102°F and purulent nasal discharge for 3 days.¹⁵

Weigh the decision to treat acute bacterial rhinosinusitis with antibiotics against the risk for potential adverse reactions and within the context of antibiotic stewardship.

Initial presentations of viral URIs and ABRS are almost identical; thus, persistence of symptoms is key to diagnosis.⁶ Nasal ­discharge tends to appear several days after initial symptoms manifest for viral infections including influenza. In children < 5 years of age, the most common complication involves the orbit.¹⁵ Orbital complications generally manifest with eye pain and/or periorbital swelling and may be accompanied by proptosis or decreased functioning of ­extraocular musculature. The differential diagnosis for orbital complications includes cavernous sinus thrombosis, orbital cellulitis/abscess, subperiosteal abscess, and inflammatory edema.^27,28 Intracranial complications are also possible with severe ABRS.¹²

Radiology studies are not recommended for the initial diagnosis of ABRS in children, as again, imaging does not differentiate between viral and bacterial etiologies. However, in children with complications such as orbital or cerebral involvement, a contrast-enhanced CT scan of the paranasal sinuses is indicated.¹⁵

Antibiotic therapy is indicated in children with a diagnosis of severe ABRS or in cases of “double sickening.” Clinicians may consider watchful waiting for 3 additional days before initiating antibiotics in patients meeting criteria for ABRS.Amoxicillin with or without clavulanate is the antibiotic of choice.¹⁵

For penicillin-allergic children without a history of anaphylactoid reaction, treatment with cefpodoxime, cefdinir, or cefuroxime is appropriate. For children with a history of anaphylaxis, treatment with a combination of clindamycin (or linezolid) and cefixime is indicated. Alternatively, a fluoroquinolone such as levofloxacin may be used, but adverse effects and emerging resistance limit its use.¹⁵

Continue to: Specialist referral

Referral to Otolaryngology is indicated for patients with > 3 episodes of clinically diagnosed bacterial sinusitis in 1 year, evidence of fungal disease (which is outside the scope of this article), immunocompromised status, or a persistent temperature ≥ 102°F despite antibiotic therapy. Also consider otolaryngology referral for patients with a history of sinus surgery.^2,5,6

CORRESPONDENCE
Pamela R. Hughes, Family Medicine Residency Clinic, Mike O’Callaghan Military Medical Center, 4700 Las Vegas Boulevard North, Nellis AFB, NV 89191; pamela.r.hughes4.mil@mail.mil.

An estimated 30 million cases of acute rhinosinusitis (ARS) occur every year in the United States.¹ More than 80% of people with ARS are prescribed antibiotics in North America, accounting for 15% to 20% of all antibiotic prescriptions in the adult outpatient setting.^2,3 Many of these prescriptions are unnecessary, as the most common cause of ARS is a virus.^4,5 Evidence consistently shows that symptoms of ARS will resolve spontaneously in most patients and that only those patients with severe or prolonged symptoms require consideration of antibiotic therapy.^1,2,4,6 Nearly half of all patients will improve within 1 week and two-thirds of patients will improve within 2 weeks without the use of antibiotics.⁷ In children, only about 6% to 7% presenting with upper respiratory symptoms meet the criteria for acute bacterial rhinosinusitis (ABRS),⁸ which we’ll detail in a bit. For most patients, treatment should consist of symptom management.⁵

But what about the minority who require antibiotic therapy? This article reviews how to evaluate patients with ARS, identify those who require antibiotics, and prescribe the most appropriate antibiotic treatment regimens.

Diagnosis: Distinguishing viral from bacterial disease

ARS is defined as the sudden onset of purulent nasal discharge plus either nasal blockage or facial pressure/pain lasting < 4 weeks.^3,9 Additional signs and symptoms may include postnasal drip, a reduced sense of smell, sinus tenderness to palpation, and maxillary toothaches.^10,11

ARS may be viral or bacterial in etiology, with the most common bacterial organisms being Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.^1,3,5 The most common viral causes are influenza, parainfluenza, and rhinovirus. Approximately 90% to 98% of cases of ARS are viral^6,11; only about 0.5% to 2% of viral rhinosinusitis episodes are complicated by bacterial infection.^1,10-12

Diagnose ABRS when symptoms of ARS fail to improve after 10 days or symptoms of ARS worsen within 10 days after initial improvement (“double sickening”).^1,11 Symptoms that are significantly associated with ABRS are unilateral sinus pain and reported maxillary pain. The presence of facial or dental pain correlates with ABRS but does not identify the specific sinus involved.¹

Approximately 90% to 98% of cases of acute rhinosinusitis are viral; only about 0.5% to 2% of viral rhinosinusitis episodes are complicated by bacterial infection.

There isn’t good correlation between patients saying they have sinusitis and actually having it.¹³ A 2019 meta-analysis by Ebell et al¹⁴ reported that based on limited data, the overall clinical impression, fetid odor on the breath, and pain in the teeth are the best individual clinical predictors of ABRS.

As recommended by the Infectious Disease Society of America (IDSA), a diagnosis of ABRS is also reasonable in patients who present with severe symptoms at the onset.⁶ Although there is no consensus about what constitutes “severe symptoms,” they are often described as a temperature ≥ 102°F (39°C) plus 3 to 4 days of purulent nasal drainage.^1,4,6

Continue to: Additional symptoms of ABRS may include...

Additional symptoms of ABRS may include cough, fatigue, decreased or lack of sense of smell (hyposmia or anosmia), and ear pressure.¹⁰ Another sign of “double sickening” is the development of a fever after several days of symptoms.^1,9,15 Viral sinusitis typically lasts 5 to 7 days with a peak at days 2 to 3.^1,15 If symptoms continue for 10 days, there is a 60% chance of bacterial sinusitis, although some viral rhinosinusitis symptoms persist for > 14 days.^1,5 Beyond 4 to 12 weeks, sinusitis is classified as subacute or chronic.³

Physical exam findings and the limited roles of imaging and labs

Common physical exam findings associated with the diagnosis of ABRS include altered speech indicating nasal obstruction; edema or erythema of the skin indicating congested capillaries; tenderness to palpation over the cheeks or upper teeth; odorous breath; and purulent drainage from the nose or in the posterior pharynx.

In a study by Hansen et al¹³ (N = 174), the only sign that showed significant association with ABRS (diagnosed by sinus aspiration or lavage) was unilateral tenderness of the maxillary sinuses. The presence of purulent drainage in the nose or posterior pharynx also has significant diagnostic value, as it predicts the presence of bacteria on antral aspiration.¹ Purulent discharge in the pharynx is associated with a higher likelihood of benefit from antibiotic therapy compared to placebo (number needed to treat [NNT] = 8).¹⁶ However, colored nasal discharge indicates the presence of neutrophils—not bacteria—and does not predict the likelihood of bacterial sinus infection.^14,17 Therefore, the history and physical exam should focus on location of pain (sinus and/or teeth), duration of symptoms, presence of fever, change in symptom severity, attempted home therapies, sinus tenderness on exam, breath odor, and purulent drainage seen in the nasal cavity or posterior pharynx.^13,14

Radiographic imaging has no role in the diagnosis or treatment of uncomplicated ABRS because viral and bacterial etiologies have similar radiographic appearances. Additionally, employing radiologic imaging would increase health care costs by at least 4-fold.^5,6,8,17 The American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) clinical practice guidelines recommend against radiographic imaging for patients who meet the diagnostic criteria for ABRS unless concern exists for a complication or an alternate diagnosis is suspected.¹ Computed tomography (CT) imaging of the sinuses may be warranted in patients with severe headaches, facial swelling, cranial nerve palsies, or bulging of the eye (proptosis), all of which indicate a potential complication of ABRS.¹

Laboratory evaluations. ABRS is a clinical diagnosis; therefore, routine lab work, such as a white blood cell count, C-­reactive protein (CRP) level, and/or erythrocyte sedimentation rate (ESR), are not indicated unless an alternate diagnosis is suspected.^1,5,13,18,19

Continue to: In one study...

In one study, CRP > 10 mg/L and ESR > 10 mm/h were the strongest individual predictors of purulent antral puncture aspirate or positive bacterial culture of aspirate, which is considered diagnostic for ABRS. ²⁰ However, CRP and ESR by themselves are not adequate to diagnose ABRS.²⁰ This study developed a clinical decision rule that used symptoms, signs, and laboratory values to rate the likelihood of ABRS as being either low, moderate, or high. However, this clinical decision rule has not been prospectively validated.

Thus, CRP and ESR elevations can support the diagnosis of ABRS, but the low sensitivity of these tests precludes their use as a screening tool for ABRS.^14,18 Studies by Ebell¹⁹ and Huang²¹ have shown some benefit to dipstick assay of nasal secretions for the diagnosis of ABRS, but this method is not validated or widely used.^19,21

Treatment: From managing symptoms to prescribing antibiotics

Overprescribing antibiotics for ARS is a prominent health care issue. In fact, 5 of 9 placebo-controlled studies showed that most people improve within 2 weeks regardless of antibiotic use (N = 1058).³ Therefore, weigh the decision to treat ABRS with antibiotics against the risk for potential adverse reactions and within the context of antibiotic stewardship.^2,9,12,22-24 Consider antibiotics only if patients meet the diagnostic criteria for ABRS (TABLE 1^1,6) or, occasionally, for patients with severe symptoms upon presentation, such as a temperature ≥ 102°F (39°C) plus purulent nasal discharge for 3 to 4 days.¹ The most commonly reported adverse effects of antibiotics are gastrointestinal in nature and include nausea, vomiting, and diarrhea.^2,9

Symptomatic management for both ARS and ABRS is recommended as first-line therapy; it should be offered to patients before making a diagnosis of ABRS.^1,5,9,25 Consider using analgesics, topical intranasal steroids, and/or nasal saline irrigation to alleviate symptoms and improve quality of life.^1,5,25 Interventions with questionable or unproven efficacy include the use of antihistamines, systemic steroids, decongestants, and mucolytics, but they may be considered on an individual basis.¹ A systematic review found that topical nasal steroids relieved facial pain and nasal congestion in patients with rhinitis and acute sinusitis (NNT = 14).^1,26

Even after diagnosing ABRS, clinicians should offer watchful waiting and symptomatic therapies as long as patients have adequate access to follow-up (TABLE 2,^1,15FIGURE^1,6). Antibiotic therapy can then be initiated if symptoms do not improve after an additional 7 days of watchful waiting or if symptoms worsen at any time. It is reasonable to give patients a prescription to keep on hand to be used if symptoms worsen, with instructions to notify the provider if antibiotics are started.¹

Continue to: Antibiotic therapy

Antibiotic therapy. The rationale for treating ABRS with antibiotics is to expedite recovery and prevent complications such as periorbital or orbital cellulitis, meningitis, frontal osteomyelitis, cavernous sinus thrombosis, and other serious illness.²⁷ Antibiotic treatment is associated with a shorter duration of symptoms (NNT = 19) but an increased risk of adverse events (NNH = 8).^7,19

Diagnose acute bacterial rhinosinusitis when symptoms of acute rhinosinusitis fail to improve after 10 days or symptoms of ARS worsen within 10 days after initial improvement.

Amoxicillin with or without clavulanate for 5 to 10 days is first-line antibiotic therapy for most adults with ABRS.^1,3,5,8,9,11 Per ­AAO-HNS, the “justification for amoxicillin as first-line treatment relates to its safety, efficacy, low cost, and narrow microbiologic spectrum.”¹ Amoxicillin may be dosed 500 mg tid for 5 to 10 days. Amoxicillin/clavulanate (Augmentin) is recommended for patients with comorbid conditions or with increased risk of bacterial resistance. Dosing for amoxicillin/clavulanate is 500/125 mg tid or 875/125 mg bid for 5 to 10 days. Duration of therapy should be determined by the severity of symptoms.⁵

For penicillin-allergic patients, doxycycline or a respiratory fluoroquinolone (levofloxacin or moxifloxacin) is considered first-line treatment.^1,6 Doxycycline is preferred because of its narrower spectrum and fewer adverse effects than the fluoroquinolones. Fluoroquinolones should be reserved for patients who fail first-line treatment and are penicillin allergic.¹ Because of the high rates of resistance among S pneumoniae and H influenzae, macrolides, trimethoprim/sulfamethoxazole (TMP/SMX), and cephalosporins are not recommended as first-line therapy.^1,5

How antibiotic options compare. A Cochrane review of 54 studies comparing different antibiotics showed no antibiotic was superior.³ Of the 54 studies, 6 studies (N = 1887) were pooled to compare cephalosporins to amoxicillin/clavulanate at 7 to 15 days. The findings indicated a statistically significant difference for amoxicillin/clavulanate with a relative risk (RR) of 1.37 (confidence interval [CI], 1.04-1.8).³ However, none of these 6 studies were graded as having a low risk of bias; therefore, confidence in this finding was deemed limited due to the quality of included studies. The failure rate for cephalosporins was 12% vs 8% for amoxicillin/clavulanate.³

Colored nasal discharge indicates the presence of neutrophils—not bacteria—and does not predict the likelihood of bacterial sinus infection.

Treatment failure is considered when a patient has not improved by Day 7 after ABRS diagnosis (with or without medication) or when symptoms worsen at any time. If watchful waiting was chosen and a safety net prescription was provided, the antibiotics should be filled and started. If no antibiotic was prescribed at the time watchful waiting commenced, the patient should return for further evaluation and be started on antibiotics. If antibiotics were prescribed initially for severe symptoms, a change in antibiotic therapy is indicated, and a broader-spectrum antibiotic should be chosen. If amoxicillin was prescribed, the patient should be switched to amoxicillin/clavulanate, doxycycline, a respiratory fluoroquinolone, or a combination of clindamycin plus a third-generation cephalosporin.¹

Continue to: Diagnosis and management of pediatric patients

Diagnosis and management of pediatric patients

Diagnosis of ABRS in children is defined as an acute upper respiratory infection (URI) accompanied by persistent nasal discharge, daytime cough for ≥ 10 days without improvement, an episode of “double sickening,” or severe onset with a temperature ≥ 102°F and purulent nasal discharge for 3 days.¹⁵

Weigh the decision to treat acute bacterial rhinosinusitis with antibiotics against the risk for potential adverse reactions and within the context of antibiotic stewardship.

Initial presentations of viral URIs and ABRS are almost identical; thus, persistence of symptoms is key to diagnosis.⁶ Nasal ­discharge tends to appear several days after initial symptoms manifest for viral infections including influenza. In children < 5 years of age, the most common complication involves the orbit.¹⁵ Orbital complications generally manifest with eye pain and/or periorbital swelling and may be accompanied by proptosis or decreased functioning of ­extraocular musculature. The differential diagnosis for orbital complications includes cavernous sinus thrombosis, orbital cellulitis/abscess, subperiosteal abscess, and inflammatory edema.^27,28 Intracranial complications are also possible with severe ABRS.¹²

Radiology studies are not recommended for the initial diagnosis of ABRS in children, as again, imaging does not differentiate between viral and bacterial etiologies. However, in children with complications such as orbital or cerebral involvement, a contrast-enhanced CT scan of the paranasal sinuses is indicated.¹⁵

Antibiotic therapy is indicated in children with a diagnosis of severe ABRS or in cases of “double sickening.” Clinicians may consider watchful waiting for 3 additional days before initiating antibiotics in patients meeting criteria for ABRS.Amoxicillin with or without clavulanate is the antibiotic of choice.¹⁵

For penicillin-allergic children without a history of anaphylactoid reaction, treatment with cefpodoxime, cefdinir, or cefuroxime is appropriate. For children with a history of anaphylaxis, treatment with a combination of clindamycin (or linezolid) and cefixime is indicated. Alternatively, a fluoroquinolone such as levofloxacin may be used, but adverse effects and emerging resistance limit its use.¹⁵

Continue to: Specialist referral

Referral to Otolaryngology is indicated for patients with > 3 episodes of clinically diagnosed bacterial sinusitis in 1 year, evidence of fungal disease (which is outside the scope of this article), immunocompromised status, or a persistent temperature ≥ 102°F despite antibiotic therapy. Also consider otolaryngology referral for patients with a history of sinus surgery.^2,5,6

CORRESPONDENCE
Pamela R. Hughes, Family Medicine Residency Clinic, Mike O’Callaghan Military Medical Center, 4700 Las Vegas Boulevard North, Nellis AFB, NV 89191; pamela.r.hughes4.mil@mail.mil.

An estimated 30 million cases of acute rhinosinusitis (ARS) occur every year in the United States.¹ More than 80% of people with ARS are prescribed antibiotics in North America, accounting for 15% to 20% of all antibiotic prescriptions in the adult outpatient setting.^2,3 Many of these prescriptions are unnecessary, as the most common cause of ARS is a virus.^4,5 Evidence consistently shows that symptoms of ARS will resolve spontaneously in most patients and that only those patients with severe or prolonged symptoms require consideration of antibiotic therapy.^1,2,4,6 Nearly half of all patients will improve within 1 week and two-thirds of patients will improve within 2 weeks without the use of antibiotics.⁷ In children, only about 6% to 7% presenting with upper respiratory symptoms meet the criteria for acute bacterial rhinosinusitis (ABRS),⁸ which we’ll detail in a bit. For most patients, treatment should consist of symptom management.⁵

But what about the minority who require antibiotic therapy? This article reviews how to evaluate patients with ARS, identify those who require antibiotics, and prescribe the most appropriate antibiotic treatment regimens.

Diagnosis: Distinguishing viral from bacterial disease

ARS is defined as the sudden onset of purulent nasal discharge plus either nasal blockage or facial pressure/pain lasting < 4 weeks.^3,9 Additional signs and symptoms may include postnasal drip, a reduced sense of smell, sinus tenderness to palpation, and maxillary toothaches.^10,11

ARS may be viral or bacterial in etiology, with the most common bacterial organisms being Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.^1,3,5 The most common viral causes are influenza, parainfluenza, and rhinovirus. Approximately 90% to 98% of cases of ARS are viral^6,11; only about 0.5% to 2% of viral rhinosinusitis episodes are complicated by bacterial infection.^1,10-12

Diagnose ABRS when symptoms of ARS fail to improve after 10 days or symptoms of ARS worsen within 10 days after initial improvement (“double sickening”).^1,11 Symptoms that are significantly associated with ABRS are unilateral sinus pain and reported maxillary pain. The presence of facial or dental pain correlates with ABRS but does not identify the specific sinus involved.¹

Approximately 90% to 98% of cases of acute rhinosinusitis are viral; only about 0.5% to 2% of viral rhinosinusitis episodes are complicated by bacterial infection.

There isn’t good correlation between patients saying they have sinusitis and actually having it.¹³ A 2019 meta-analysis by Ebell et al¹⁴ reported that based on limited data, the overall clinical impression, fetid odor on the breath, and pain in the teeth are the best individual clinical predictors of ABRS.

As recommended by the Infectious Disease Society of America (IDSA), a diagnosis of ABRS is also reasonable in patients who present with severe symptoms at the onset.⁶ Although there is no consensus about what constitutes “severe symptoms,” they are often described as a temperature ≥ 102°F (39°C) plus 3 to 4 days of purulent nasal drainage.^1,4,6

Continue to: Additional symptoms of ABRS may include...

Additional symptoms of ABRS may include cough, fatigue, decreased or lack of sense of smell (hyposmia or anosmia), and ear pressure.¹⁰ Another sign of “double sickening” is the development of a fever after several days of symptoms.^1,9,15 Viral sinusitis typically lasts 5 to 7 days with a peak at days 2 to 3.^1,15 If symptoms continue for 10 days, there is a 60% chance of bacterial sinusitis, although some viral rhinosinusitis symptoms persist for > 14 days.^1,5 Beyond 4 to 12 weeks, sinusitis is classified as subacute or chronic.³

Physical exam findings and the limited roles of imaging and labs

Common physical exam findings associated with the diagnosis of ABRS include altered speech indicating nasal obstruction; edema or erythema of the skin indicating congested capillaries; tenderness to palpation over the cheeks or upper teeth; odorous breath; and purulent drainage from the nose or in the posterior pharynx.

In a study by Hansen et al¹³ (N = 174), the only sign that showed significant association with ABRS (diagnosed by sinus aspiration or lavage) was unilateral tenderness of the maxillary sinuses. The presence of purulent drainage in the nose or posterior pharynx also has significant diagnostic value, as it predicts the presence of bacteria on antral aspiration.¹ Purulent discharge in the pharynx is associated with a higher likelihood of benefit from antibiotic therapy compared to placebo (number needed to treat [NNT] = 8).¹⁶ However, colored nasal discharge indicates the presence of neutrophils—not bacteria—and does not predict the likelihood of bacterial sinus infection.^14,17 Therefore, the history and physical exam should focus on location of pain (sinus and/or teeth), duration of symptoms, presence of fever, change in symptom severity, attempted home therapies, sinus tenderness on exam, breath odor, and purulent drainage seen in the nasal cavity or posterior pharynx.^13,14

Radiographic imaging has no role in the diagnosis or treatment of uncomplicated ABRS because viral and bacterial etiologies have similar radiographic appearances. Additionally, employing radiologic imaging would increase health care costs by at least 4-fold.^5,6,8,17 The American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) clinical practice guidelines recommend against radiographic imaging for patients who meet the diagnostic criteria for ABRS unless concern exists for a complication or an alternate diagnosis is suspected.¹ Computed tomography (CT) imaging of the sinuses may be warranted in patients with severe headaches, facial swelling, cranial nerve palsies, or bulging of the eye (proptosis), all of which indicate a potential complication of ABRS.¹

Laboratory evaluations. ABRS is a clinical diagnosis; therefore, routine lab work, such as a white blood cell count, C-­reactive protein (CRP) level, and/or erythrocyte sedimentation rate (ESR), are not indicated unless an alternate diagnosis is suspected.^1,5,13,18,19

Continue to: In one study...

In one study, CRP > 10 mg/L and ESR > 10 mm/h were the strongest individual predictors of purulent antral puncture aspirate or positive bacterial culture of aspirate, which is considered diagnostic for ABRS. ²⁰ However, CRP and ESR by themselves are not adequate to diagnose ABRS.²⁰ This study developed a clinical decision rule that used symptoms, signs, and laboratory values to rate the likelihood of ABRS as being either low, moderate, or high. However, this clinical decision rule has not been prospectively validated.

Thus, CRP and ESR elevations can support the diagnosis of ABRS, but the low sensitivity of these tests precludes their use as a screening tool for ABRS.^14,18 Studies by Ebell¹⁹ and Huang²¹ have shown some benefit to dipstick assay of nasal secretions for the diagnosis of ABRS, but this method is not validated or widely used.^19,21

Treatment: From managing symptoms to prescribing antibiotics

Overprescribing antibiotics for ARS is a prominent health care issue. In fact, 5 of 9 placebo-controlled studies showed that most people improve within 2 weeks regardless of antibiotic use (N = 1058).³ Therefore, weigh the decision to treat ABRS with antibiotics against the risk for potential adverse reactions and within the context of antibiotic stewardship.^2,9,12,22-24 Consider antibiotics only if patients meet the diagnostic criteria for ABRS (TABLE 1^1,6) or, occasionally, for patients with severe symptoms upon presentation, such as a temperature ≥ 102°F (39°C) plus purulent nasal discharge for 3 to 4 days.¹ The most commonly reported adverse effects of antibiotics are gastrointestinal in nature and include nausea, vomiting, and diarrhea.^2,9

Symptomatic management for both ARS and ABRS is recommended as first-line therapy; it should be offered to patients before making a diagnosis of ABRS.^1,5,9,25 Consider using analgesics, topical intranasal steroids, and/or nasal saline irrigation to alleviate symptoms and improve quality of life.^1,5,25 Interventions with questionable or unproven efficacy include the use of antihistamines, systemic steroids, decongestants, and mucolytics, but they may be considered on an individual basis.¹ A systematic review found that topical nasal steroids relieved facial pain and nasal congestion in patients with rhinitis and acute sinusitis (NNT = 14).^1,26

Even after diagnosing ABRS, clinicians should offer watchful waiting and symptomatic therapies as long as patients have adequate access to follow-up (TABLE 2,^1,15FIGURE^1,6). Antibiotic therapy can then be initiated if symptoms do not improve after an additional 7 days of watchful waiting or if symptoms worsen at any time. It is reasonable to give patients a prescription to keep on hand to be used if symptoms worsen, with instructions to notify the provider if antibiotics are started.¹

Continue to: Antibiotic therapy

Antibiotic therapy. The rationale for treating ABRS with antibiotics is to expedite recovery and prevent complications such as periorbital or orbital cellulitis, meningitis, frontal osteomyelitis, cavernous sinus thrombosis, and other serious illness.²⁷ Antibiotic treatment is associated with a shorter duration of symptoms (NNT = 19) but an increased risk of adverse events (NNH = 8).^7,19

Diagnose acute bacterial rhinosinusitis when symptoms of acute rhinosinusitis fail to improve after 10 days or symptoms of ARS worsen within 10 days after initial improvement.

Amoxicillin with or without clavulanate for 5 to 10 days is first-line antibiotic therapy for most adults with ABRS.^1,3,5,8,9,11 Per ­AAO-HNS, the “justification for amoxicillin as first-line treatment relates to its safety, efficacy, low cost, and narrow microbiologic spectrum.”¹ Amoxicillin may be dosed 500 mg tid for 5 to 10 days. Amoxicillin/clavulanate (Augmentin) is recommended for patients with comorbid conditions or with increased risk of bacterial resistance. Dosing for amoxicillin/clavulanate is 500/125 mg tid or 875/125 mg bid for 5 to 10 days. Duration of therapy should be determined by the severity of symptoms.⁵

For penicillin-allergic patients, doxycycline or a respiratory fluoroquinolone (levofloxacin or moxifloxacin) is considered first-line treatment.^1,6 Doxycycline is preferred because of its narrower spectrum and fewer adverse effects than the fluoroquinolones. Fluoroquinolones should be reserved for patients who fail first-line treatment and are penicillin allergic.¹ Because of the high rates of resistance among S pneumoniae and H influenzae, macrolides, trimethoprim/sulfamethoxazole (TMP/SMX), and cephalosporins are not recommended as first-line therapy.^1,5

How antibiotic options compare. A Cochrane review of 54 studies comparing different antibiotics showed no antibiotic was superior.³ Of the 54 studies, 6 studies (N = 1887) were pooled to compare cephalosporins to amoxicillin/clavulanate at 7 to 15 days. The findings indicated a statistically significant difference for amoxicillin/clavulanate with a relative risk (RR) of 1.37 (confidence interval [CI], 1.04-1.8).³ However, none of these 6 studies were graded as having a low risk of bias; therefore, confidence in this finding was deemed limited due to the quality of included studies. The failure rate for cephalosporins was 12% vs 8% for amoxicillin/clavulanate.³

Colored nasal discharge indicates the presence of neutrophils—not bacteria—and does not predict the likelihood of bacterial sinus infection.

Treatment failure is considered when a patient has not improved by Day 7 after ABRS diagnosis (with or without medication) or when symptoms worsen at any time. If watchful waiting was chosen and a safety net prescription was provided, the antibiotics should be filled and started. If no antibiotic was prescribed at the time watchful waiting commenced, the patient should return for further evaluation and be started on antibiotics. If antibiotics were prescribed initially for severe symptoms, a change in antibiotic therapy is indicated, and a broader-spectrum antibiotic should be chosen. If amoxicillin was prescribed, the patient should be switched to amoxicillin/clavulanate, doxycycline, a respiratory fluoroquinolone, or a combination of clindamycin plus a third-generation cephalosporin.¹

Continue to: Diagnosis and management of pediatric patients

Diagnosis and management of pediatric patients

Diagnosis of ABRS in children is defined as an acute upper respiratory infection (URI) accompanied by persistent nasal discharge, daytime cough for ≥ 10 days without improvement, an episode of “double sickening,” or severe onset with a temperature ≥ 102°F and purulent nasal discharge for 3 days.¹⁵

Weigh the decision to treat acute bacterial rhinosinusitis with antibiotics against the risk for potential adverse reactions and within the context of antibiotic stewardship.

Initial presentations of viral URIs and ABRS are almost identical; thus, persistence of symptoms is key to diagnosis.⁶ Nasal ­discharge tends to appear several days after initial symptoms manifest for viral infections including influenza. In children < 5 years of age, the most common complication involves the orbit.¹⁵ Orbital complications generally manifest with eye pain and/or periorbital swelling and may be accompanied by proptosis or decreased functioning of ­extraocular musculature. The differential diagnosis for orbital complications includes cavernous sinus thrombosis, orbital cellulitis/abscess, subperiosteal abscess, and inflammatory edema.^27,28 Intracranial complications are also possible with severe ABRS.¹²

Radiology studies are not recommended for the initial diagnosis of ABRS in children, as again, imaging does not differentiate between viral and bacterial etiologies. However, in children with complications such as orbital or cerebral involvement, a contrast-enhanced CT scan of the paranasal sinuses is indicated.¹⁵

Antibiotic therapy is indicated in children with a diagnosis of severe ABRS or in cases of “double sickening.” Clinicians may consider watchful waiting for 3 additional days before initiating antibiotics in patients meeting criteria for ABRS.Amoxicillin with or without clavulanate is the antibiotic of choice.¹⁵

For penicillin-allergic children without a history of anaphylactoid reaction, treatment with cefpodoxime, cefdinir, or cefuroxime is appropriate. For children with a history of anaphylaxis, treatment with a combination of clindamycin (or linezolid) and cefixime is indicated. Alternatively, a fluoroquinolone such as levofloxacin may be used, but adverse effects and emerging resistance limit its use.¹⁵

Continue to: Specialist referral

Referral to Otolaryngology is indicated for patients with > 3 episodes of clinically diagnosed bacterial sinusitis in 1 year, evidence of fungal disease (which is outside the scope of this article), immunocompromised status, or a persistent temperature ≥ 102°F despite antibiotic therapy. Also consider otolaryngology referral for patients with a history of sinus surgery.^2,5,6

CORRESPONDENCE
Pamela R. Hughes, Family Medicine Residency Clinic, Mike O’Callaghan Military Medical Center, 4700 Las Vegas Boulevard North, Nellis AFB, NV 89191; pamela.r.hughes4.mil@mail.mil.