Once-Weekly Oral Islatravir-Lenacapavir Maintains HIV-1 Viral Suppression at 48 Weeks
In 607 adults with virologically suppressed HIV-1, once-weekly oral ISL/LEN was noninferior to once-daily B/F/TAF at week 48. HIV-1 RNA levels of 50 copies/mL or higher occurred in 0% versus 0.3% of participants, respectively. Virologic suppression, CD4+ T-cell changes, and safety outcomes were comparable between the groups.
KEY FINDINGS: Once-weekly oral ISL/LEN was noninferior to once-daily B/F/TAF for maintaining virologic suppression through week 48 in adults with previously suppressed HIV-1. No participants receiving ISL/LEN had HIV-1 RNA levels of 50 copies/mL or higher, and virologic suppression rates remained high in both treatment groups. CD4+ T-cell changes and safety outcomes were broadly comparable. The once-weekly oral regimen may provide a less frequent treatment option for patients who prefer oral therapy but may benefit from reduced dosing frequency.
BACKGROUND: Daily single-tablet antiretroviral regimens have substantially improved HIV-1 management; however, maintaining long-term adherence remains challenging for some patients. Less frequent oral treatment schedules may provide an alternative to daily therapy while avoiding the need for injectable regimens. This phase 3 trial evaluated the efficacy and safety of once-weekly oral islatravir-lenacapavir (ISL/LEN) in adults with virologically suppressed HIV-1.
DETAILS: This phase 3, double-blind, randomized, active-controlled, noninferiority trial was conducted in 12 countries. Adults with HIV-1 viral suppression for at least 6 months while receiving once-daily bictegravir-emtricitabine-tenofovir alafenamide (B/F/TAF) were randomly assigned in a 1:1 ratio to switch to once-weekly oral ISL/LEN (2 mg/300 mg) or continue once-daily B/F/TAF for 96 weeks. The primary endpoint was the proportion of participants with HIV-1 RNA levels of 50 copies/mL or higher at week 48, assessed using the FDA-defined snapshot algorithm. The prespecified noninferiority margin was 4 percentage points. A total of 607 participants underwent randomization, including 304 assigned to ISL/LEN and 303 assigned to B/F/TAF. At week 48, no participants in the ISL/LEN group and 1 participant (0.3%) in the B/F/TAF group had HIV-1 RNA levels of 50 copies/mL or higher (difference, -0.3 percentage points; 95.002% CI, -1.4 to 0.8), meeting the criterion for noninferiority. HIV-1 RNA levels below 50 copies/mL were observed in 284 participants (93.4%) receiving ISL/LEN and 280 participants (92.4%) receiving B/F/TAF (difference, 1.0 percentage point; 95% CI, -3.2 to 5.2). The mean change in CD4+ T-cell count was -10 cells/µL with ISL/LEN and -18 cells/µL with B/F/TAF, with a least-squares mean difference of 12 cells/µL (95% CI, -16 to 39). Treatment discontinuation due to adverse events occurred in 6 participants (2.0%) receiving ISL/LEN and 5 participants (1.7%) receiving B/F/TAF; serious adverse events occurred in 16 participants (5.3%) and 14 participants (4.6%), respectively.
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Broad-Spectrum Antibiotic Use Is Lower Among Hospice Patients With Cancer at the End of Life
In this nationwide Korean cohort, hospice utilization was associated with lower broad-spectrum antibiotic use as death approached, particularly during the final week and final 3 days of life. The findings suggest that hospice involvement may be associated with a transition toward more selective antimicrobial use and less intensive treatment near the end of life. However, the study was observational, and causality cannot be established. Important clinical variables, including infection severity, microbiological findings, functional status, symptom burden, cancer stage, and treatment intent, were unavailable in the claims data.
KEY FINDINGS: Among adults with cancer approaching death, hospice utilization was associated with less frequent and lower-intensity broad-spectrum antibiotic exposure, particularly during the final days of life. The findings are consistent with a transition toward comfort-focused care, although they do not establish that hospice care itself caused the reduction. Hospice initiation occurred relatively close to death, with a mean interval of 39.9 days and a median of 22.0 days, and some antibiotic treatment may have preceded hospice enrollment. In addition, cancer stage, treatment status, infection severity, microbiological findings, functional status, symptom burden, and treatment intent were unavailable in the claims data.
BACKGROUND: Antibiotic treatment remains common during end-of-life care for patients with cancer, despite uncertain benefits for survival and potential burdens including drug toxicity, intravenous administration, adverse effects, and antimicrobial resistance. This retrospective cohort study evaluated whether hospice involvement was associated with differences in broad-spectrum antibiotic use among adults with cancer during the final 3 months of life.
DETAILS: Investigators analyzed Korean National Health Insurance Service claims data for adults aged ≥18 years who died between January 1, 2018, and December 31, 2021, with one of the 10 leading cancer-related causes of death. Hospice users had received inpatient, home-based, or consultation-based hospice care before death. Broad-spectrum antibiotic exposure included anti-pseudomonal penicillins, anti-pseudomonal cephalosporins, carbapenems, and glycopeptides. The final 90 days of life were divided into four intervals: 1–3 months before death, 1 week to 1 month before death, the final week, and the final 3 days. Antibiotic exposure was assessed by the proportion of patients receiving antibiotics and by days of therapy (DOT) per 1,000 patient-days. Propensity score matching was performed at a 1:2 ratio.
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After matching, 38,102 hospice users and 75,736 non-hospice users were analyzed. During the final 3 months of life, 74.6% of hospice users and 79.0% of non-hospice users received at least one broad-spectrum antibiotic (P0.001). Antibiotic use was initially slightly higher among hospice users during the period 1–3 months before death, at 34.0% versus 32.2% (P0.001), but became consistently lower among hospice users thereafter. From 1 week to 1 month before death, use was 31.1% versus 32.8%; during the final week, 11.3% versus 18.5%; and during the final 3 days, 4.8% versus 10.3% among hospice and non-hospice users, respectively (all P0.001).
Days of therapy per 1,000 patient-days were also consistently lower among hospice users, with the greatest differences occurring during the final week and final 3 days of life. Carbapenems and glycopeptides demonstrated particularly pronounced differences between the groups. In cancer-specific analyses, patients with hematologic malignancies had the highest overall antibiotic exposure, followed by those with pancreatobiliary and gastric cancers, while exposure was comparatively lower among patients with breast and liver cancers.
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Source: Jeung, Y. S., Kim, H. J., Yu, J., et al. Comparison of Broad-Spectrum Antibiotic Use According to Hospice Utilization Among Patients with Cancer at the End of Life in South Korea: A Nationwide Analysis. Journal of Hospice and Palliative Care. 2026; 29(2): 41-50. Published: June 1, 2026. DOI: 10.14475/jhpc.2026.29.2.41.
US Measles Cases Rise in 2026 as Outbreaks Continue Amid Declining MMR Coverage
US measles activity has increased substantially in 2026, with 2,465 confirmed cases and 38 new outbreaks reported as of August 6. Declining MMR coverage may increase community vulnerability to transmission. Maintaining high vaccination coverage remains central to preventing measles outbreaks and sustaining elimination.
KEY FINDINGS: As of August 6, 2026, the US had reported 2,465 confirmed measles cases and 38 new outbreaks, with 94% of cases outbreak-associated. The increase occurs alongside a decline in kindergarten MMR coverage to 92.5% in 2024-2025 from 95.2% in 2019-2020. CDC emphasizes that measles can spread rapidly in communities with lower vaccination coverage, while 2 doses of MMR vaccine provide 97% protection against measles.
BACKGROUND: Measles was officially eliminated in the United States in 2000 following widespread use of the measles, mumps, and rubella (MMR) vaccine. However, declining vaccination coverage and increasing global measles activity have increased opportunities for measles transmission following importation into the United States.
DETAILS: As of August 6, 2026, the Centers for Disease Control and Prevention (CDC) reported 2,465 confirmed measles cases in the United States in 2026. Of these, 2,449 cases were reported by 47 jurisdictions, while 16 cases occurred among international visitors to the United States. Thirty-eight new outbreaks had been reported during 2026.
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Overall, 94% of confirmed cases in 2026 (2,309 of 2,465) were associated with outbreaks, including 936 cases from outbreaks beginning in 2026 and 1,373 from outbreaks that began in 2025. For comparison, 2,289 confirmed cases and 48 outbreaks were reported during the full year of 2025; 90% of cases (2,066 of 2,289) were outbreak-associated.
CDC reports confirmed measles cases notified by jurisdictions as of noon on Thursdays. An outbreak is defined as 3 or more related cases. State and CDC counts may differ because jurisdictions update and publicly report their data on different schedules.
MMR vaccination coverage among US kindergartners declined from 95.2% during the 2019-2020 school year to 92.5% during the 2024-2025 school year, leaving approximately 286,000 kindergartners at risk during the 2024-2025 school year. CDC notes that communities with vaccination coverage below the 95% level are more vulnerable to measles outbreaks. The 2026 measles case count reported by CDC as of August 6, 2026, had already exceeded the total number of confirmed cases reported during all of 2025 (2,465 vs 2,289). The high proportion of outbreak-associated cases indicates sustained transmission within affected communities.
The burden of measles remains closely associated with vaccination status. CDC reports that 2 doses of MMR vaccine are 97% effective at preventing measles, while 1 dose is 93% effective. Breakthrough infections can occur, particularly during outbreaks with high levels of circulating measles virus, and account for approximately 10% of all measles infections.
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Source: CDC: Measles Cases and Outbreaks. Centers for Disease Control and Prevention (CDC). 2026; Published: August 7, 2026.
Global Forecasts Reveal Rising Antimicrobial Resistance Threats in Children
Global pediatric antimicrobial resistance increased from 2004 to 2022 across all regions. Resistance was highest among Gram-negative pathogens, children in intensive care, those with sepsis, and resource-limited settings. By 2035, carbapenem resistance is projected to reach 35% in Klebsiella species and 82% in Acinetobacter baumannii.
KEY FINDINGS: This global pediatric surveillance study demonstrates a sustained increase in antimicrobial resistance among children, with the greatest concern involving Gram-negative pathogens, intensive care settings, sepsis cases, and resource-limited regions. Increasing resistance to Watch and Reserve antibiotics may compromise treatment options for severe childhood infections. Forecasted growth in carbapenem resistance among Klebsiella species and Acinetobacter baumannii highlights the need for strengthened antimicrobial stewardship, surveillance systems, and development of effective pediatric treatment strategies.
BACKGROUND: Antimicrobial resistance (AMR) threatens the effectiveness of antibiotic therapy for severe childhood infections, yet comprehensive pediatric AMR surveillance data across multiple regions remain limited. This study evaluated global and temporal patterns of antimicrobial resistance among children using the World Health Organization (WHO) Access, Watch, and Reserve (AWaRe) antibiotic classification framework and projected future resistance trends
DETAILS: This cross-sectional surveillance study analyzed pediatric bacterial isolates from the Antimicrobial Testing Leadership and Surveillance (ATLAS) database collected between January 2004 and December 2022. The study included 106 581 isolates from 106 581 children aged 0 to 18 years across 82 countries. Data were analyzed from February 2024 to April 2026. Resistance trends were assessed by geographic region, age group, clinical setting, infection syndrome, and pathogen type, with spatiotemporal models used to forecast resistance patterns through 2035.
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The analysis categorized antibiotics according to the WHO AWaRe framework: Access antibiotics used for first-line treatment, Watch antibiotics with higher resistance potential, and Reserve antibiotics intended for difficult-to-treat infections. The study evaluated WHO priority pathogens and examined resistance patterns among different pediatric populations, including children with sepsis and respiratory infections.
From 2004 to 2022, pediatric AMR increased across all regions, with higher resistance levels and faster increases observed in resource-limited settings. Resistance to Access-group antibiotics was highest overall, with a mean resistance of 36% (range, 2%-66%), compared with Watch-group antibiotics at a mean of 22% (range, 1%-47%) and Reserve-group antibiotics at a mean of 13% (range, 0%-30%).
Resistance to higher-tier antibiotics increased substantially in vulnerable clinical groups. In intensive care units, Watch-group resistance increased from 15% (517/3564) to 33% (2910/8748) (P < .001), particularly among children aged 0 to 2 years, where resistance increased from 12% (325/2649) to 32% (1257/3959) (P < .001). Among children with sepsis, Watch-group resistance increased from 15% (298/2030) to 30% (1409/4705) (P < .001), while Reserve-group resistance increased from 3% (16/474) to 26% (746/2824) (P < .001).
Among critical pathogens, Acinetobacter baumannii demonstrated the highest overall resistance, exceeding 55% in every AWaRe antibiotic category in 2022. Klebsiella species showed the fastest increases in resistance, particularly to third- or fourth-generation cephalosporins and carbapenems. Forecasts estimated that by 2035, carbapenem resistance would reach 35% (95% uncertainty interval [UI], 29%-40%) in Klebsiella species and 82% (95% UI, 77%-85%) in A baumannii.
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Source: Hu, Y. J., Qiu, H., Harwell, J. I., et al. Childhood Antimicrobial Resistance With Global Forecasts. JAMA Pediatrics. 2026; Published: July 20, 2026. DOI: 10.1001/jamapediatrics.2026.2808.
Promising Drug Candidates and Emerging Therapeutic Strategies Against Candida auris
Emerging therapies for Candida auris extend beyond conventional antifungal agents and include repurposed drugs, novel antifungal compounds, vaccines, antimicrobial peptides, and nanotechnology-based approaches. While further clinical validation is needed, these strategies may help address the growing challenge of multidrug-resistant C. auris infections.
KEY FINDINGS: This review underscores the expanding pipeline of therapeutic strategies targeting Candida auris, ranging from repurposed medications and next-generation antifungal agents to vaccines, antimicrobial peptides, nanoparticle formulations, and innovative environmental control measures. Although no single therapy has emerged as a definitive solution, compounds such as ibrexafungerp (SCY-078), ATI-2307, and fosmanogepix, together with drug repurposing and bioinspired approaches, represent promising avenues for addressing multidrug-resistant C. auris infections. Continued translational research and clinical evaluation remain essential to establish safe and effective treatment options for this increasingly important fungal pathogen.
BACKGROUND: Candida auris has rapidly emerged as a multidrug-resistant fungal pathogen of global concern since its first identification in 2009. The organism is associated with healthcare-associated outbreaks, high transmissibility, frequent misidentification, and severe invasive infections, with reported mortality rates ranging from 35% to 72%. Resistance to currently available antifungal agents further complicates treatment, with approximately 90% of isolates resistant to fluconazole, around 30% resistant to amphotericin B, and fewer than 5% resistant to echinocandins. These challenges have accelerated efforts to identify novel antifungal therapies and alternative treatment strategies.
DETAILS: This publication is a comprehensive narrative review that summarizes advances in antifungal research targeting C. auris over the preceding decade. The authors evaluated emerging therapeutic approaches from a medicinal chemistry perspective, including drug repurposing, combination therapy, novel antifungal agents, natural products, metal-based compounds, nanoparticles, vaccines, antimicrobial peptides, and environmental decontamination strategies. The review also examined chemical and physicochemical characteristics of promising compounds, including lipophilicity and topological polar surface area, to identify structural features that may facilitate future antifungal drug development. The review highlights several promising therapeutic candidates with activity against multidrug-resistant C. auris. Drug repurposing identified multiple agents with antifungal or antibiofilm activity, including sertraline, miltefosine, iodoquinol, octenidine dihydrochloride, taurolidine, and bensulfuron methyl. Miltefosine demonstrated fungicidal and antibiofilm activity, while encapsulation within alginate nanoparticles reduced toxicity and improved survival in an infected Galleria mellonella model. The NDV-3A vaccine generated cross-reactive antibodies against C. auris and protected neutropenic mice, with additive efficacy when combined with micafungin.
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Among novel antifungal agents, SCY-078 (ibrexafungerp), an orally available 1,3-ß-D-glucan synthesis inhibitor, demonstrated potent activity against C. auris, with an MIC90 of 1 mg/L and MIC50 and MIC90 values of 0.5 µg/mL and 1 µg/mL, respectively, across 100 isolates representing the four major clades. More than 150 strains with diverse resistance profiles were subsequently shown to be uniformly susceptible to SCY-078, and the agent remained active against pan-resistant isolates while also exhibiting antibiofilm activity.
Additional investigational therapies also demonstrated encouraging preclinical activity. The arylamidine T-2307 (ATI-2307) exhibited in vitro MIC values ranging from 0.125 to 4 µg/mL and improved survival while reducing kidney fungal burden in murine infection models following 3 mg/kg once-daily subcutaneous treatment. Other experimental approaches included antimicrobial peptides, ceragenins, fluorinated hydrazone derivatives, and novel chemical scaffolds designed to overcome existing resistance mechanisms.
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Source: Billamboz, M., Fatima, Z., Hameed, S., et al. Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris. Microorganisms. 2021; 9(3): 634. Published: March 18, 2021. DOI: 10.3390/microorganisms9030634.
Ambulatory Antibiotic Prescribing for Acute Sinusitis
Overall, approximately one-third of patients with acute sinusitis did not meet guideline-based indications for antibiotic therapy, yet antibiotics continued to be prescribed frequently in this population. These findings highlight opportunities for antimicrobial stewardship initiatives to improve both prescribing frequency and treatment duration, particularly in clinical settings where adherence to recommended practices is suboptimal, while monitoring potential unintended effects such as repeat healthcare utilization.
Summary
Multicenter Evaluation Reveals Persistent Gaps in Guideline-Concordant Care
[Posted 8/Jul/2026]
AUDIENCE: Infectious Disease, Internal Medicine
KEY FINDINGS: This multicenter evaluation demonstrates that antibiotic prescribing for acute sinusitis remains substantially higher than recommended by evidence-based guidelines, with nearly one-third of patients failing to meet prescribing criteria and fewer than half of prescriptions fully adhering to recommended antibiotic selection and duration. Prolonged symptom duration, cough, and incomplete documentation were significant drivers of inappropriate prescribing, while electronic encounters were associated with more judicious antibiotic use. These findings identify important opportunities for antimicrobial stewardship interventions aimed at improving prescribing decisions and optimizing treatment duration in ambulatory care.
BACKGROUND: Acute sinusitis is among the most common indications for antibiotic prescribing in ambulatory practice, despite national guidelines recommending antibiotic therapy only when specific clinical criteria suggest bacterial infection. Inappropriate antibiotic use contributes to adverse drug events, antimicrobial resistance, and unnecessary healthcare expenditures. This multicenter study evaluated the appropriateness of antibiotic prescribing for acute sinusitis, assessed concordance with guideline-recommended agent selection and treatment duration, and identified factors associated with inappropriate prescribing.
DETAILS: This retrospective multicenter cohort study included 1,000 randomly selected adult ambulatory encounters with a primary diagnosis of acute sinusitis between January 1, 2024, and March 31, 2024. Encounters were drawn from emergency departments, urgent care centers, and primary care clinics across seven geographic regions within a large healthcare system. Medical records were reviewed to determine whether patients met national guideline criteria for antibiotic therapy based on symptom duration, severe symptoms, treatment failure, or double worsening. Antibiotic selection and treatment duration were evaluated against institutional recommendations. Multivariable logistic regression was performed to identify predictors of inappropriate antibiotic prescribing, and 30-day repeat respiratory-related healthcare utilization was also assessed. Among the 1,000 encounters, 676 (67.6%) met guideline criteria for antibiotic therapy, whereas 324 (32.4%) did not. Antibiotics were prescribed in 892 (89.2%) encounters overall. Prescribing occurred in 93.5% of encounters meeting treatment criteria but also in 80.2% of encounters where criteria were not satisfied, indicating substantial antibiotic use beyond guideline recommendations. Overall, only 49.2% of antibiotic prescriptions were fully guideline concordant with respect to both agent selection and duration. Guideline-concordant drug selection occurred in 74.1% of prescriptions, while 64.5% met recommended treatment duration. The most frequently prescribed antibiotic was amoxicillin/clavulanate (60.9%), followed by doxycycline (19.1%), and the median treatment duration was 7 days. However, 35.4% of patients received therapy lasting longer than 7 days. Watch-and-wait prescribing was used in only 6.8% of antibiotic-treated encounters. Multivariable analysis demonstrated that the presence of cough (OR 2.15; 95% CI, 1.08-4.29; P = 0.03), symptom duration of 7-9 days compared with 6 days (OR 7.70; 95% CI, 3.24-18.31; P 0.001), and undocumented symptom duration (OR 5.01; 95% CI, 1.41-17.82; P = 0.013) were independently associated with inappropriate antibiotic prescribing. In contrast, electronic encounters were associated with significantly lower odds of inappropriate prescribing than in-person visits (OR 0.03; 95% CI, 0.01-0.09; P 0.001). Unplanned respiratory-related healthcare contact within 30 days occurred in 12.8% of patients and was more frequent among those who did not receive antibiotics (20.4% vs 11.9%; P = 0.013), although antibiotic prescribing was not independently associated with reduced repeat healthcare utilization after multivariable adjustment.
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Source: Arensman Hannan, K., Ilges, D., Le, K. T., Cole K, et al. Ambulatory antibiotic prescribing for acute sinusitis: a multicenter, retrospective cohort study evaluating appropriateness. Antimicrobial Stewardship & Healthcare Epidemiology.. 2026; 6(1): e193. Published: June 25, 2026. DOI: 10.1017/ash.2026.10743.
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