As of late January 2026, the United States is facing an aggressive surge in respiratory infections. The dominant pathogen is influenza A – specifically a highly mutated variant of H3N2 known as subclade K, which currently accounts for over 90% of U.S. cases. Because subclade K emerged after the 2025-2026 vaccine was finalized, we are seeing significant antigenic drift and high infection rates, even in vaccinated populations. The current influenza positivity rate is 18%, compared to 5.3% for COVID-19. The pre-test probability for influenza A in patients presenting with sudden-onset respiratory distress is exceptionally high. Read more about the current outbreak in my last post on this influenza season.
The Golden Rule: Empiric Treatment
In the urgent care setting, your clinical judgment often outpaces the laboratory. Per Centers for Disease Control and Prevention (CDC) guidance, do not wait for test results to start antivirals in high-risk patients; if a patient presents with suspected influenza, initiate treatment.
Defining the High-Risk Population
Who is officially considered “high risk”? The CDC’s definition is specific and includes adults aged ≥65 years, children aged <5 years (and especially those aged <2 years), and patients who are pregnant or up to 2 weeks postpartum. It also includes patients with chronic conditions (eg, asthma, chronic obstructive pulmonary disease [COPD], heart disease, diabetes mellitus) and immunocompromised patients. For all of these populations, the risk of complications such as pneumonia is significantly higher.
Navigating the Negative Result
What if that high-risk patient’s rapid antigen test is negative? Do not be misled. Because of the moderate sensitivity of rapid influenza diagnostic tests (RIDTs), a negative result does not rule out influenza during peak circulation. If your suspicion is high, especially in a patient with a COPD or asthma flare, continue empiric treatment regardless of that negative result.
The Low-Risk Outpatient
Testing is optional for previously healthy, low-risk patients; if influenza is widespread in your community, a clinical diagnosis is sufficient. Testing is only indicated if the result will change your management plan, such as prescribing antivirals within the 48-hour window or protecting high-risk household contacts.
Clinical Suspicion
How do you know to suspect influenza before the swab? Clinical signs are your first clues. Unlike many respiratory viruses that start with a slow creep, influenza typically hits suddenly. Be alert for rapid onset of high fever, intense myalgia, and profound fatigue. A patient who felt fine at breakfast but is bedridden by lunch is the classic influenza presentation.
It can be tough to differentiate based on symptoms alone, so look for the nuances. Influenza is more often associated with a “sudden hit” of body aches, while symptoms typically emerge more gradually in COVID-19; however, COVID-19 is more likely to involve prolonged fatigue and/or a new loss of taste or smell, which are rare with influenza. Common colds are generally milder and dominated by upper airway congestion and runny nose.
Current Context: January 2026 Data
Context matters. As of late January 2026, we are seeing high levels of influenza activity nationwide. In contrast, COVID-19 test positivity rates are currently low. While COVID-19 remains a factor, the high influenza-to-COVID ratio means that any sudden “flu-like illness” that occurs right now has a high pretest probability for influenza.
Testing
Rapid Antigen Tests (RIDTs)
Rapid antigen tests target viral nucleoproteins. These tests are fast (10-15 minutes) and available as point-of-care or over-the-counter home tests. While specificity is high (90%-95%), sensitivity is only moderate (typically 50%-70%). Remember that in high-prevalence settings, a negative antigen test does not rule out infection.
Rapid Molecular (NAATs)
Rapid molecular nucleic acid amplification tests (NAATs), such as those using LAMP or NEAR technology, provide results in 15 to 30 minutes with significantly higher sensitivity (around 90%-95%) than RIDTs, approaching that of laboratory-based polymerase chain reaction (PCR) tests. They are the preferred point-of-care choice for most outpatient settings. Many NAATs provide simultaneous testing for influenza and COVID-19.
Lab-Based PCR
PCR testing is the gold standard. These are laboratory-based and often multiplexed for influenza A and B along with COVID-19. Expect a turnaround time of 45 minutes to several hours for in-house tests, or 1 to 3 days if sent out. Both sensitivity and specificity are ≥98%.
Performance Comparison Table for Reference
| Test Type | Technology | Sensitivity | Specificity | Turnaround Time |
|---|---|---|---|---|
| Antigen (RIDT) | Immunoassay | 50–70% | 90–95% | 10–15 Minutes |
| Rapid NAAT | LAMP / NEAR | 90–95% | >95% | 15–30 Minutes |
| Lab RT-PCR | Molecular | >98% | >99% | 45 Min – 3 Days |
Treatment
The Big Four
There are 4 FDA-approved antivirals for use in high-risk patients with confirmed or strongly suspected influenza. In the outpatient setting, oseltamivir, baloxavir, and zanamivir are used most often. The fourth option (peramivir), which is administered as a single-dose IV infusion, is typically reserved for patients who cannot tolerate oral or inhaled medications.
Oseltamivir (Tamiflu®) Versus Baloxavir (Xofluza®)
Oseltamivir is a workhorse. It is a neuraminidase inhibitor approved for all ages, including infants, and is the preferred choice in patients who are pregnant or breastfeeding. The primary drawbacks are its 5-day course and common gastrointestinal side effects such as nausea and vomiting. Baloxavir, on the other hand, is a cap-dependent endonuclease inhibitor administered in a single dose and approved for patients aged ≥5 years. While it is more convenient than oseltamivir, it is not recommended for pregnant or breastfeeding patients due to lack of data.
Zanamivir (Relenza®) and Peramivir (Rapivab®)
Zanamivir is an inhaled powder approved for patients aged ≥7 years. It is an excellent option for patients who cannot swallow pills, but it is strictly contraindicated in patients who have underlying airway disease (eg, asthma or COPD), due to the risk of bronchospasm. Peramivir is available only for IV administration and is approved for patients aged ≥6 months. While it is a single dose, the IV formulation limits its use outside of hospital settings.
Renal Adjustments and Dialysis
Oseltamivir and peramivir require dosage modifications based on creatinine clearance. For patients on hemodialysis, oseltamivir is typically dosed after sessions. Baloxavir and zanamivir do not require renal adjustment, making them simpler options for patients with chronic kidney disease, though clinical data for patients on dialysis are still limited.
Immunocompromised Strategy
The CDC recommends oseltamivir over baloxavir for immunocompromised patients. These patients often experience prolonged viral shedding, so be prepared for a longer treatment course.
Baloxavir Marboxil (Xofluza®) Prescribing Details
- Minimum age: 5 years
- Time window from symptom onset: 48 hrs
- Caution: “Use caution with coadministration of products containing polyvalent cations due to reduced exposure.” That means if you are taking Xofluza®, you should avoid the following for a few hours before and after your dose:
- Dairy Products: Milk, cheese, yogurt, or calcium-fortified orange juice.
- Antacids: Tums™ (calcium), Maalox™/Mylanta™ (magnesium/aluminum)
- Supplements: Multivitamins, iron pills, or zinc lozenges
- Laxatives: Many contain magnesium
- Special Populations:
- Pregnancy: No
- Breastfeeding: No
- Renal insufficiency (CrCl < 50 mL/min) / Dialysis: No
Osetlamivir (Tamiflu®) Prescribing Details
- Minimum age: 2 weeks
- Time window from symptom onset: 48 hrs
- Caution: Oral suspension contains sorbitol; use caution in hereditary fructose intolerance.
- Special Populations:
Peramivir (Rapivab®) Prescribing Details
- Minimum age: 6 months
- Time window from symptom onset: 48 hrs
- Caution Use caution due to risk of serious skin reactions and anaphylaxis.
- Special Populations:
- Pregnancy: No
- Breastfeeding: No
- Renal insufficiency / Dialysis: See Chart
Zanamivir (Relenza®) Prescribing Details
- Minimum age: 7 years
- Time window from symptom onset: 48 hrs
- Caution: Avoid in patients with milk protein allergy. Avoid in asthma or COPD due to bronchospasm risk. Use caution in patients with underlying airway disease.
- Special Populations:
- Pregnancy: No
- Breastfeeding: No
- Renal insufficiency or Dialysis: No dose adjustment
Last Updated on February 2, 2026
Sam Ashoo, MD, FACEP, is board certified in emergency medicine and clinical informatics. He serves as EB Medicine’s editor-in-chief of interactive clinical pathways and FOAMEd blog, and host of EB Medicine’s EMplify podcast. Follow him below for more…
