Practice Changing Updates

INTRODUCTION — 

This section highlights selected specific new recommendations and/or updates that we anticipate may change usual clinical practice. Practice Changing Updates focus on changes that may have significant and broad impact on practice, and therefore do not represent all updates that affect practice. These Practice Changing Updates, reflecting important changes to UpToDate over the past year, are presented chronologically, and are discussed in greater detail in the identified topic reviews.

INFECTIOUS DISEASES (May 2025, Modified August 2025)

Chikungunya vaccination in travelers

●When chikungunya vaccination is indicated, we recommend recombinant virus-like particle over live-attenuated virus vaccine because of potential safety signals of the live-attenuated virus vaccine (Grade 1C).

Chikungunya virus is a growing public health concern; travelers frequently acquire infection and can import the virus into new areas. Apart from avoiding mosquito exposure, vaccination is the primary preventive strategy:

•In 2025, the US Food and Drug Administration (FDA) approved and the Centers for Disease Control and Prevention (CDC) recommended recombinant virus-like particle (VLP) chikungunya vaccine (VIMKUNYA) for selected high-risk travelers aged 12 years and older [1,2]; approval was based on several trials demonstrating high seroconversion rates.

•Reports of serious adverse effects in older adults following receipt of the previously approved live-attenuated virus chikungunya vaccine (IXCHIQ) prompted several regulatory agencies to restrict use in older adults or advise caution [3,4]. In the United States, the FDA withdrew approval of the live-attenuated virus chikungunya vaccine [5].

When indicated, we recommend the recombinant VLP over the live-attenuated virus vaccine; if the recombinant VLP vaccine is unavailable, the live-attenuated virus vaccine may be used in immunocompetent adults <60 years old. (See "Chikungunya fever: Treatment and prevention", section on 'Indication and choice of vaccine'.)

ONCOLOGY (August 2025)

Aspirin for stage I to III PIK3CA-mutated colorectal cancer

●For patients with stage I to III colorectal cancer and a somatic (tumoral) phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation who have completed surgery, we suggest aspirin (Grade 2C), at a dose of 160 mg orally daily, to be continued for three years.

For patients with treated stage I to III colorectal cancer (CRC) and a somatic (tumoral) phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation, studies are evaluating the benefits of aspirin. In preliminary results of a placebo-controlled randomized trial of over 600 patients with stage I to III PIK3CA-mutated colorectal cancer who completed surgery, low-dose aspirin (160 mg daily) for three years reduced the recurrence rate (hazard ratio 0.45; 8 versus 14 percent for those with PIK3CA mutations in exon 9 or 20) [6]. Among those with other PI3K pathway alterations, it reduced recurrence rates (8 versus 17 percent) and improved three-year disease-free survival (89 versus 79 percent). For patients with stage I to III CRC who complete surgery and have a somatic PIK3CA mutation, we now suggest low-dose aspirin, to be continued for three years. (See "Adjunctive therapy for non-metastatic treated colorectal cancer: Aspirin, NSAIDs, and vitamin D", section on 'PIK3CA mutations'.)

INFECTIOUS DISEASES (July 2025)

Updated guidelines for prophylaxis after a nonoccupational exposure to HIV

●For most people who initiate nonoccupational post-exposure prophylaxis to prevent HIV, we suggest bictegravir-emtricitabine-tenofovir alafenamide (Grade 2C).

People who present within 72 hours of a possible nonoccupational exposure to human immunodeficiency virus (HIV) should be evaluated for post-exposure prophylaxis with antiretroviral therapy (nPEP). If indicated, updated guidelines from the United States Centers for Disease Control and Prevention suggest bictegravir-emtricitabine-tenofovir alafenamide or dolutegravir plus either tenofovir alafenamide or tenofovir disoproxil fumarate [7]. Previously, tenofovir alafenamide had been avoided for nPEP, particularly for exposure through vaginal sex, but emerging indirect data from pre-exposure prophylaxis trials support its use. For most people, we suggest bictegravir-emtricitabine-tenofovir alafenamide since it is administered as a single pill once daily. There may be additional considerations for regimen selection in those with reduced kidney function or exposure to drug-resistant HIV. (See "Management of nonoccupational exposures to HIV and hepatitis B and C in adults", section on 'Preferred regimens'.)

PULMONARY AND CRITICAL CARE MEDICINE (June 2025)

Add-on therapy for refractory COPD in patients with peripheral eosinophilia

●For patients with COPD and peripheral eosinophilia (≥300 cells/microL) who have recurrent exacerbations despite triple inhaled therapy, we suggest the addition of dupilumab or mepolizumab rather than other therapies (Grade 2C).

The use of biologics targeting type 2 inflammation in chronic obstructive pulmonary disease (COPD) has demonstrated promise, with approval of dupilumab in 2024 and new approval of mepolizumab for patients with eosinophilia and exacerbations despite inhaled therapies. Mepolizumab approval followed a trial of over 800 patients with COPD, peripheral hypereosinophilia (≥300 cells/microL), and exacerbations despite triple inhaled therapy (long-acting muscarinic antagonist, long-acting beta agonist, and inhaled corticosteroid). Those randomized to treatment with the anti-interleukin 5 monoclonal antibody mepolizumab (100 mg subcutaneously monthly) had a reduction in moderate or severe exacerbations compared with placebo (0.80 versus 1.01 events per year), but no improvements in lung function or respiratory symptoms [8]. Similar patients treated with dupilumab have shown a somewhat larger reduction in exacerbation rates and modest improvements in lung function and symptoms. Absent comparative trials, we now suggest either dupilumab or mepolizumab for patients with COPD and peripheral eosinophilia who have persistent exacerbations despite optimized inhaled therapy (algorithm 1). (See "Management of refractory chronic obstructive pulmonary disease", section on 'Mepolizumab'.)

PULMONARY AND CRITICAL CARE MEDICINE (June 2025)

Methotrexate as initial therapy for symptomatic, moderate-to-severe pulmonary sarcoidosis

●For most symptomatic patients with pulmonary sarcoidosis who have severe lung involvement, worsening radiographic opacities, or increasing pulmonary function impairment, we suggest initial treatment with methotrexate rather than glucocorticoid therapy, observation alone, or other alternative therapies (Grade 2C).

Pulmonary sarcoidosis is usually treated initially with oral glucocorticoids, which have numerous side effects. In a new open-label trial of 138 treatment-naïve patients with pulmonary sarcoidosis and moderate-to-severe symptoms, impaired lung function, or disease progression over the last 12 months, patients randomly assigned to weekly oral methotrexate monotherapy for 24 weeks had similar lung function improvement compared with patients assigned to prednisone (6.2 versus 5.7 percentage point improvement in predicted forced vital capacity) [9]. Methotrexate had a slower onset of action but was associated with less weight gain (1.1 versus 5.0 kg) and similar patient satisfaction by the end of the trial. Based in part on this evidence, we now suggest methotrexate as initial therapy for most patients with moderate-to-severe pulmonary sarcoidosis requiring treatment; concurrent oral glucocorticoids are appropriate for those with rapidly progressing disease. (See "Treatment of pulmonary sarcoidosis: Initial approach", section on 'Efficacy of methotrexate'.)

NEUROLOGY (May 2025)

No benefit of mechanical thrombectomy for acute stroke due to medium vessel occlusion

●For patients with acute ischemic stroke due to a medium vessel occlusion (MeVO; ie, middle cerebral artery beyond the proximal dominant M2 segment, anterior cerebral artery beyond the A1 segment, or posterior cerebral artery beyond the P1 segment), we recommend against routine treatment with mechanical thrombectomy (Grade 1B).

Data from multiple randomized clinical trials have established the benefit of mechanical thrombectomy (MT) for acute ischemic stroke due to large vessel occlusion (LVO). However, there was no high-quality evidence to support the use of MT for patients with acute stroke due to medium vessel occlusion (MeVO), generally defined as the middle cerebral artery beyond the proximal dominant M2 segment, the anterior cerebral artery beyond the A1 segment, and the posterior cerebral artery beyond the P1 segment. This situation has changed with new data from the recent ESCAPE-MeVO and DISTAL trials [10,11]. Both trials failed to demonstrate the benefit of MT for patients with acute ischemic stroke due to MeVO, and the ESCAPE-MeVO trial found that MT increased mortality [10]. Given these data, we recommend against routine treatment with MT for patients with acute ischemic stroke due to a MeVO. Regardless of whether they are candidates for MT, eligible patients should still receive standard treatment with intravenous thrombolysis. (See "Mechanical thrombectomy for acute ischemic stroke", section on 'Medium and distal vessel occlusion'.)

INFECTIOUS DISEASES (May 2025)

Tecovirimat not effective for mpox

●For most immunocompetent patients with mpox, we suggest not using antiviral therapy (Grade 2B). In patients with severe disease (eg, encephalitis, pneumonitis) or highly immunocompromised patients at risk for severe disease, we suggest combination antiviral therapy with tecovirimat and either brincidofovir or cidofovir (Grade 2C).

The antiviral tecovirimat has been used for patients with or at risk for severe mpox based on animal studies and observational studies in humans. However, in a randomized clinical trial of mostly immunocompetent people in Africa with clade 1 mpox infection, there were no differences in time to lesion healing (7 versus 8 days), mortality, or pregnancy outcomes with tecovirimat compared with placebo [12]. Preliminary data from a trial evaluating tecovirimat in patients with clade 2 disease demonstrated similar findings [13]. We now suggest not using antiviral therapy for most immunocompetent patients with mpox. For highly immunocompromised patients and those with severe disease (eg, encephalitis or pneumonitis), we suggest tecovirimat plus another antiviral; although monotherapy with tecovirimat does not appear effective for mpox, its role in combination antiviral therapy has not been evaluated. (See "Treatment and prevention of mpox (formerly monkeypox)", section on 'Tecovirimat'.)

PRIMARY CARE (ADULT) (March 2025)

Male partner treatment to prevent recurrence of bacterial vaginosis

●For male sex partners of female patients with confirmed bacterial vaginosis, we suggest simultaneous dual oral and topical antibiotic treatment rather than no treatment or single-drug treatment (Grade 2C), in order to reduce recurrent infection in female patients.

Treatment of male sex partners to reduce bacterial vaginosis (BV) recurrence in females is an area of ongoing study. In a trial of 150 male-female monogamous couples with confirmed BV in the female, treatment of the male partner for one week with an oral and topical antibiotic (metronidazole tablet and clindamycin cream) in addition to standard antimicrobial treatment of the female patient reduced recurrences at 12 weeks compared with treating the female patient only (35 versus 63 percent; risk difference -2.6 recurrences per person-year) [14]. Based on these results, we now suggest dual topical and oral antimicrobial male partner therapy as an effective strategy to reduce BV recurrence in female patients. (See "Bacterial vaginosis: Initial treatment", section on 'Males'.)

ALLERGY AND IMMUNOLOGY (February 2025)

Egg allergy no longer a concern for any vaccines

●Hen's egg allergy is no longer a reason to withhold yellow fever vaccine or any other vaccine, including influenza, measles, mumps, and rubella (MMR), and rabies.

Some vaccines contain trace amounts of egg protein (table 1), but none contain enough to cause reactions in egg-allergic patients. For the last several years, it has been recommended that patients not be asked about egg allergy prior to receiving influenza vaccine. More recently, data have accumulated to show that egg allergy is similarly not a concern for administration of the yellow fever vaccine. In the largest study to date, 171 children with egg allergy, including 24 percent with a history of anaphylaxis, underwent skin testing with the yellow fever vaccine and then received it regardless of skin test results, with no allergic reactions [15]. Thus, we no longer inquire about egg allergy prior to the administration of any vaccine. Vaccine providers should remain prepared to treat rare allergic reactions that may occur after any vaccine, but no special precautions are necessary for recipients with egg allergy. (See "Allergic reactions to vaccines", section on 'Hen's egg'.)

INFECTIOUS DISEASES (January 2025)

Updated United States guidelines on perinatal HIV transmission

●For infants born to women who have maintained a viral load <50 copies/mL on antiretroviral therapy (ART) from 20 weeks gestation through delivery, we suggest two weeks of prophylaxis with zidovudine (Grade 2C). For infants born to mothers who have viremia (HIV RNA level ≥50 copies/mL, either documented or presumed) at the time of, or in the four weeks prior to delivery, we recommend presumptive therapy with a three-drug antiretroviral regimen (Grade 1B). For all others, we engage in shared decision-making to decide between these two approaches.

The United States Department of Health and Human Services has updated the perinatal HIV clinical guidelines [16]. They now categorize infants born to mothers with HIV into three risk stratification groups based on maternal HIV viral load during pregnancy, the most significant risk factor for transmission. The lowest-risk infants are born to mothers with sustained viral suppression (HIV RNA <50 copies/mL) since 20 weeks gestation. The highest-risk infants are born to mothers with a detectable HIV viral load within four weeks of delivery. All other infants fall into the middle-risk category. This risk stratification informs the antiretroviral regimen given to the infant to prevent HIV transmission, outlined in the table (table 2). Our approach to the management of infants exposed to HIV at birth is consistent with these updated guidelines. (See "Management of infants born to mothers with HIV in resource-abundant settings", section on 'Approach to ARV drug management'.)

INFECTIOUS DISEASES (November 2024)

Lower age cutoff for pneumococcal vaccine indications

●We recommend pneumococcal vaccination for all adults ≥65 years old and adults <65 years old who are at risk for pneumococcal infection or severe complications from pneumococcal infection (Grade 1B). We also suggest pneumococcal vaccination for all adults between 50 to 64 years of age (Grade 2C).

In October 2024, the United States Advisory Committee (ACIP) extended pneumococcal vaccination recommendations to include all adults ≥50 years of age, regardless of risk factors (table 3) [17]. Previously, the age threshold was ≥65 years for healthy adults and ≥19 years for those at risk for pneumococcal infection or severe complications from pneumococcal infection. This decision is based on knowledge that the incidence of pneumococcal disease starts to increase at age 50 (table 4) and the predicted reduction in invasive pneumococcal disease cases in certain underrepresented ethnic/racial groups within the United States. We agree with the new guidelines from the ACIP and now suggest pneumococcal vaccination beginning at age 50 for all adults. (See "Pneumococcal vaccination in adults", section on 'Indications for vaccination'.)

EMERGENCY MEDICINE (ADULT AND PEDIATRIC) (October 2024)

Preoxygenation before pediatric procedural sedation

●For children undergoing procedural sedation, we suggest against the use of preoxygenation (Grade 2C).

Use of preoxygenation prior to pediatric procedural sedation varies across institutions and providers, and the benefits are unclear. In a new multicenter retrospective study of nearly 85,600 sedations recorded in the Pediatric Sedation Research Consortium database, preprocedural oxygenation (performed in 51 percent of sedations) was not associated with reduced need for airway/breathing/circulation intervention during sedation [18]. In other experience, potential harms of preoxygenation include delayed recognition of hypoventilation and increased anxiety and discomfort related to the administration of oxygen in infants and young children. Based on these data, we now suggest against the use of preprocedural oxygenation for children undergoing procedural sedation. (See "Procedural sedation in children: Approach", section on 'Preoxygenation'.)

INFECTIOUS DISEASES (September 2024)

PCV21 for pneumococcal vaccination

●For choice of vaccine in patients who have not received prior pneumococcal vaccines, we suggest PCV21 (Grade 2C) rather than PCV20 alone or PCV15 followed by PPSV23.

For pneumococcal vaccination in the United States, pneumococcal conjugate vaccine 20 (PCV20) alone or PCV15 followed by pneumococcal polysaccharide vaccine 23 (PPSV23) have been the preferred options. In 2024, the Advisory Committee on Immunization Practices (ACIP) updated guidance on pneumococcal vaccination to include pneumococcal conjugate vaccine 21 (PCV21) alone as an additional option [19]. Since PCV21 contains eleven serotypes that are common causes of invasive pneumococcal disease in adults that are absent from PCV20 (figure 1), we now suggest PCV21 for most adults with indications for pneumococcal vaccination (table 3). However, for individuals at increased risk for serotype 4 infection (eg, residents of Navajo nation or individuals residing in the Western United States and Canada who have substance use disorder or experience homelessness), we prefer to administer PCV20 (or PCV15 followed by PPSV23 if PCV20 is not available) rather than PCV21, which does not contain serotype 4. (See "Pneumococcal vaccination in adults", section on 'Approach to adults without history of pneumococcal vaccination'.)

CARDIOVASCULAR MEDICINE (September 2024)

Mineralocorticoid receptor antagonists for heart failure with preserved ejection fraction

●In patients with HFpEF receiving optimal therapy with a diuretic and a sodium-glucose co-transporter 2 inhibitor with or without semaglutide who have persistent NYHA class II to III heart failure symptoms, we suggest adding a mineralocorticoid receptor antagonist (MRA) (Grade 2C). In order to start an MRA (spironolactone, eplerenone, or finerenone) patients should be at low risk for hyperkalemia and have intact kidney function.

The role of mineralocorticoid receptor antagonists (MRA) in the treatment of heart failure with preserved ejection fraction (HFpEF) has been unclear. In a recent randomized trial in over 6000 patients with heart failure (HF) and left ventricular ejection fraction ≥40 percent, patients receiving the MRA finerenone had a lower rate of acute HF episodes than those receiving placebo over a median of 32 months [20]. Though the effect on worsening HF was small, these results are consistent with those previously reported from a controversial trial of spironolactone. In patients receiving optimal therapy with a diuretic and a sodium-glucose co-transporter 2 inhibitor with or without semaglutide and who have persistent New York Heart Association class II to III HF symptoms, we now suggest adding an MRA (algorithm 2). (See "Treatment and prognosis of heart failure with preserved ejection fraction", section on 'Secondary therapy (MRA)'.)

GENERAL SURGERY (August 2024)

Small versus large bite technique for continuous closure of midline laparotomy incisions

●For patients with body mass index (BMI) ≤30 kg/m² undergoing continuous closure of a midline laparotomy incision, we recommend a 5 mm suture width and interval rather than the conventional technique of 10 mm suture width and interval (Grade 1B).

Midline laparotomy incisions are generally closed with a continuous suture, but the suture width and interval have not been standardized. In a randomized trial of 173 patients with an average body mass index (BMI) of 26 kg/m², the small bite technique (5 mm suture width and interval) reduced both the rate of incisional hernia at one year (7 versus 27 percent) and two years (9 versus 31 percent), and the rate of surgical site infection (18 versus 31 percent) compared with the large bite technique (10 mm suture width and interval) [21]. Based on these and previous data, we recommend a small bite technique for fascial closure in patients with a <BMI. Since a benefit has not been demonstrated in patients with obesity (ie, BMI ≥30 kg/m²), the closure technique in these patients is determined by patient anatomy and surgeon preference. (See "Principles of abdominal wall closure", section on 'Continuous closure technique'.)