What's Hot This Year in ID Clinical Science 2025

Abstract

The diversity and depth of clinical research in the field of infectious diseases in 2025 were impressive. Multiple new antibiotics were approved, innovative uses of technology to improve patient care were tested, and novel approaches were trialed to address longstanding problems in infectious diseases. Despite this progress, the resurgence of measles in 2025 offers a stark reminder that any progress against infectious diseases can quickly be lost if the principles of infectious diseases and public health are abandoned. Some of the most important clinical trials and trends in infectious diseases over the past year are highlighted in this review.

This review covers notable public health trends and clinical trials covering a broad range of infectious diseases topics from October 2024 to September 2025. These updates were highlighted in the “What's Hot in ID Clinical Science” session at ID Week 2025.

Despite the unprecedented challenges facing public health and infectious diseases (ID) research, 2025 still saw many notable advancements in ID clinical science through the publication of practice-changing randomized clinical trials (RCTs) and the approval of new antibiotics. The “What's Hot in ID Clinical Science” session at the annual IDWeek meeting offered an opportunity to reflect on some of the notable studies published in the past year; although, there were many more excellent studies than could be presented in the time allowed. In this review, we highlight the topics that were included for presentation at IDWeek 2025 in Atlanta, GA, based on a combination of their clinical relevance, methodological rigor, and potential to influence practice.

NEW ANTIBIOTICS WITH FDA APPROVAL

Three new antibiotics received approval by the US Food and Drug Administration (FDA) this past year, all of which were supported by recently published trials. Aztreonam–avibactam is a monobactam/β-lactamase inhibitor combination antibiotic that was approved by the FDA for the treatment of complicated intra-abdominal infections (cIAIs) in February 2025. Designed for metallo-β-lactamase (MBL) producing organisms, two recent studies examined its use. The REVISIT trial randomized 422 patients with confirmed or suspected cIAIs or hospital-acquired or ventilator-associated pneumonias (HAP or VAP) to receive either aztreonam-avibactam with or without metronidazole or meropenem with or without colistin [1]. The study looked at a primary outcome of clinical cure at a test of cure visit 28 days after enrollment and found the overall clinical response rate in the two arms was relatively comparable (68.4% in the aztreonam-avibactam group, 65.7% in the meropenem group); although no formal noninferiority testing was conducted. Only 10 patients had infections with MBL-producing organisms, however. The ASSEMBLE trial randomized patients confirmed to have infections due to MBL-producing organisms to receive either aztreonam–avibactam or the best available therapy [2]. Only 15 patients were able to be randomized in this study, but it found favorable responses to aztreonam–avibactam, as well. Together, these studies suggest aztreonam-avibactam is a viable option for infections due to MBL-producing bacteria.

Sulopenem, which received FDA approval in October 2024, is a first-in-class thiopenem and the first approved oral penem. After failing to meet noninferiority criteria in previous studies examining its use in urinary tract infections (UTIs) [3, 4], sulopenem also failed to meet noninferiority when compared to ertapenem for cIAI [5]. It did, however, demonstrate noninferiority versus amoxicillin–clavulanate for the treatment of uncomplicated UTIs [6].

The first-in-class triazaacenaphthylene antibiotic, gepotidacin, inhibits DNA replication through distinct binding sites and was approved in March 2025. Although it was FDA-approved as another oral option for uncomplicated UTIs, the EAGLE-1 RCT published this year also found gepotidacin to be noninferior to intramuscular ceftriaxone with oral azithromycin for uncomplicated urogenital gonorrhea [7].

Despite their current FDA indications, it is unclear if sulopenem and gepotidacin have any role to play in treating uncomplicated infections. Instead, it is likely these antibiotics will find a niche in the treatment of infections due to resistant organisms where oral options are limited.

TREATING BACTERIAL INFECTIONS

Several trials published in 2025 offered novel approaches to treating bacterial infections. Dalbavancin is a long-acting lipoglycopeptide that offers an alternative to prolonged intravenous (IV) antibiotics, particularly for the treatment of Staphylococcus aureus, but data on its use for bacteremia were limited. The DOTS RCT randomized 200 patients with S. aureus bacteremia to either 2 doses of IV dalbavancin 1 week apart or to standard therapy of 4–8 weeks of IV antibiotics [8]. Patients with left-sided endocarditis, implanted medical devices that were not going to be removed, hepatic insufficiency, and severe immunosuppression were excluded from this study. Despite the use of a desirability of outcome ranking endpoint, dalbavancin did not prove superior. The secondary outcome of clinical efficacy at day 70 did demonstrate noninferiority of dalbavancin based on a noninferiority margin of 20%, supporting its use as a potential alternative to prolonged IV antibiotics in certain cases of S. aureus bacteremia.

While fecal microbiota transplantation (FMT) has been shown to be a useful treatment for recurrent Clostridioides difficile infections (CDIs), an RCT published in 2025 tested it as a primary treatment for CDIs without the use of antibiotics [9]. The study was terminated early after a prespecified interim analysis demonstrated noninferiority of FMT by a noninferiority margin of 25%. In the 104 patients randomized to receive either 10 days of oral vancomycin or a one-time enema administered FMT, the primary outcome of clinical cure with only the assigned treatment at day 14 and no recurrence of CDI for 60 days was met in 67% of the FMT group versus 61% of the vancomycin group (difference 5.4, 95% CI −13.5 to 24.4). This difference was largely driven by an increased rate of recurrence in the vancomycin group, which was 21.1% versus 5.6% in the FMT group.

Bacterial vaginosis (BV) is a common dysbiosis of the vaginal microbiota with high rates of recurrence. While prior trials involving the treatment of male partners with oral antibiotics had not shown any benefit, the StepUp RCT published in 2025 randomized 164 females with BV and their heterosexual partners to either female-only treatment or to a partner-treatment group [10]. Males in the partner treatment group received 7 days of oral metronidazole and topical clindamycin cream applied twice daily to the penis, in addition to their female partners receiving treatment. Notably, this was an open-labeled study, and there was no use of placebo cream in the control group. The study was terminated early after female treatment alone was found to be inferior at an interim analysis, with the primary outcome of recurrence of BV within 12 weeks occurring in 35% of the partner treatment group versus 63% of the female-only treatment group for a hazard ratio of 0.37. While the impact of treating male partners was significant in this study, the real-world impact may be more limited, as partner treatment strategies can be difficult to implement.

ANTIMICROBIAL STEWARDSHIP

A large focus of antimicrobial stewardship is reducing unnecessary antibiotic use by using the shortest duration of antibiotics necessary. Several studies published in 2025 focused on determining appropriate antibiotic durations. With over 3600 patients across 7 countries, the BALANCE RCT was the largest and most inclusive known study of antibiotic durations in bacteremia [11]. With just a few exclusion criteria (most notably patients with S. aureus bacteremia, severe immunocompromise, or having other established reasons for prolonged treatment courses), this study was able to randomize a diverse patient population to either 7 or 14 days of antibiotics. The study was nonblinded, so 23% of patients in the 7-day group received a longer duration of antibiotics than planned. For the primary outcome of 90-day all-cause mortality, 7 days of antibiotics was noninferior to 14 days, both by the intention-to-treat analysis (14.5% vs 16.1%; difference −1.6%; 95% CI −4.0% to 0.8%) and per-protocol analysis (13.0% vs 15.0%; difference −2.0%; 95% CI −4.5% to 0.6%). These findings were consistent across many different subgroups and pathogens, supporting 7 days as the appropriate duration of antibiotics for most cases of bacteremia due to bacteria other than S. aureus in immunocompetent adults. These results help further the movement towards shorter, evidence-based antibiotic courses in infectious syndromes that have traditionally received longer treatment durations.

The ADAPT-Sepsis RCT took a more personalized approach and compared the use of biomarkers, specifically C-reactive protein (CRP) or procalcitonin, to determine the minimal antibiotic duration necessary for patients with sepsis [12]. A total of 2761 patients with suspected sepsis admitted to critical/intensive care units (ICU) were randomized to either standard care, daily CRP, or daily procalcitonin. Antibiotic discontinuation was recommended based on the absolute value of the biomarkers or the relative decrease from baseline values measured within the first 24 hours of IV antibiotics. The procalcitonin-guided group showed a significant reduction in the primary outcome of total antibiotic duration and was noninferior with regard to 28-day all-cause mortality, while the CRP-guided group did not show a reduction in antibiotic duration nor could it be determined to be noninferior with regard to mortality.

Looking specifically at children with febrile UTIs, the INDI-UTI RCT randomized 408 children ages 3 months to 12 years to either 10 days of antibiotics or an individualized treatment plan where antibiotics were discontinued based on symptom resolution [13]. Patients in the individualized arm had antibiotics stopped 3 days after resolution of flank pain, dysuria, and fever, which resulted in significantly fewer antibiotic days within 28 days of treatment initiation (6 vs 10 days). UTI recurrence within 28 days after the end of treatment did not meet the noninferiority margin, with 11% recurrence in the individualized group versus 6% in the 10-day treatment group (difference 5.3, 95% CI −∞ to 11.1). There were also fewer antibiotic-related adverse events in the individualized treatment group, making the application of these opposing findings in the two primary outcomes challenging. Further research to delineate who is at increased risk of recurrence would be beneficial.

USING TECHNOLOGY TO IMPROVE ID CARE

In a world that is increasingly interconnected and reliant on computers and electronic health records, there are many opportunities to utilize technology to improve healthcare, and ID is no exception.

The INSPIRE 3 and INSPIRE 4 studies, both published in 2025, were two studies in a series looking at the use of computerized provider order entry (CPOE) prompts to help reduce the use of empiric extended-spectrum antibiotics by providing providers with patient and pathogen-specific estimates of multidrug-resistant organism (MDRO) infection risk [14, 15]. These cluster randomized trials looked at the use of CPOE prompts in skin and soft tissue infections and abdominal infections. The same 92 hospitals were randomized to either the CPOE bundle arm or the routine stewardship arm for both trials. There were 60 725 patients in the skin and soft tissue infection study and 105 004 in the abdominal infection study over the 12-month intervention period. Models assessing over 60 variables were used to predict which patients had an absolute MDRO risk <10%, and those patients' providers received prompts recommending standard spectrum antibiotics along with other antimicrobial stewardship education. Both studies showed significant reductions in their primary outcome of days of extended-spectrum antibiotics per patient during the first 3 hospital days, with relative reductions of 27.5% (skin and soft tissue infections) and 35% (abdominal infections), respectively. This occurred without evidence of increases in hospital length of stay or need for ICU transfer. These studies support the use of models and CPOE prompts to help providers make antimicrobial decisions that are beneficial for both patients and antimicrobial stewardship.

Technology has also revolutionized how we can provide healthcare, allowing the delivery of specialized care via telemedicine. A unique application of telemedicine was studied in the Peer TeleHCV RCT [16]. The burden of disease due to Hepatitis C virus (HCV) disproportionately affects people who use drugs and who live in rural areas where access to care is limited. In this study, 203 people, from 7 rural counties in Oregon, who use drugs, and had HCV viremia were randomized to either peer-assisted telemedicine HCV treatment or enhanced usual care that included peer-assisted referral to local providers. The primary outcome of HCV viral clearance at 12 weeks was seen in 63% of participants in the peer-assisted telemedicine group versus only 16% in the enhanced usual care (relative risk 4.06, 95% CI 2.52 to 6.52). Overall, treatment was initiated in 85% of patients in the intervention group versus just 12% in the control group. This was despite a study population in which 70% of participants had experienced houselessness in the past 6 months and over 80% had used injection drugs in the past 30 days. This model of delivering HCV care has the potential to have significant impact on the HCV epidemic and other diseases impacting patients in similar settings.

The recently published NUDGE-FLU-CHRONIC RCT examined the use of behaviorally informed electronic letters to increase influenza vaccination rates [17]. This pragmatic study enrolled all Danish citizens between ages 18 and 64 years with at least 1 pre-existing chronic disease. The 299 881 study participants were automatically randomized to receive usual care or one of six different behaviorally informed electronic letters designed to increase uptake of free-of-charge vaccination. The letters all included standard information about the risks associated with influenza in patients with chronic diseases, the patient's eligibility to get vaccinated, and the benefits of vaccination against influenza. The percentage of patients receiving influenza vaccination increased in all patients receiving letters, and a repeat letter 10 days later led to the highest vaccination rate (41.8% vs 27.9% in the usual care arm). While this is an easy and affordable intervention leading to a significant increase in influenza vaccination rates, the overall vaccination rate remained less than 50% in this higher-risk population, suggesting room for further improvement.

VACCINES

Preventing infections using vaccines remains one of the most effective interventions in infectious diseases, and continued research is needed to develop solutions for infections that have traditionally lacked vaccine strategies. The rVSV-ZEBOV live vaccine, the first approved vaccine against Ebola, was tested in a ring vaccination strategy during a 2018–2020 outbreak in the Democratic Republic of Congo [18]. A total of 1853 rings were formed, covering over 95% of the 3323 laboratory confirmed cases, resulting in over 300 000 vaccinations. There was no control group in this study for ethical reasons, making it difficult to separate the effect of vaccination from case isolation and other infection-control measures; however, contacts who were vaccinated within 0–8 days of an index case showed a reduced rate of developing Ebola versus those who received vaccination 9 or more days after index case onset. The results of this strategy of vaccinating rings of contacts and contacts-of-contacts around patients with Ebola during an outbreak are encouraging as they demonstrate the feasibility of implementing a large-scale ring vaccination strategy even under difficult and resource-limited conditions.

With over 1500 cases, 2025 has seen the greatest incidence of measles in the United States in 30 years [19]. There have also been 3 deaths from measles in the United States this year, the first in 10 years. The United States is in danger of losing its measles elimination status, which is not surprising given that the rates of MMR vaccination among kindergarteners have dropped below the 95% required for herd immunity in most states [19]. A recent study modeling the spread of vaccine-preventable infectious diseases across the United States used data on area-specific estimates for demography, population immunity, and infectious diseases importation risk to modeled scenarios assuming different vaccination rates over a 25-year period [20]. The simulation model found that measles cases, due to the very high basic reproduction number of the disease, will increase exponentially with even just a slight further decline in vaccination rates. A drop in vaccination rates by just 10% was predicted to lead to measles becoming endemic again within a decade. Encouragingly, the model also suggested that an increase in vaccination rates by 5% could prevent this outcome, suggesting it is not too late to intervene.

TUBERCULOSIS

Tuberculosis remains the biggest global infectious cause of mortality, with the prevalence of multidrug-resistant (MDR) tuberculosis increasing. Given the difficulty in treating MDR tuberculosis, strategies to prevent its spread are of great interest. Two recent studies looked at the use of levofloxacin for this purpose. The VQUIN RCT conducted in Vietnam randomized participants living with persons who had a confirmed diagnosis of either rifampicin-resistant or MDR tuberculosis to receive either 6 months of daily oral levofloxacin or placebo [21]. The 2041 household contacts who were randomized were of all ages and had evidence of M. tuberculosis infection (as evident by a positive TST) but no evidence of tuberculosis disease. The TB-CHAMP RCT was conducted exclusively in children in South Africa living in households with exposure to an adult with confirmed MDR tuberculosis [22]. Any patient under the age of 5 without evidence of tuberculosis disease could be enrolled, but only children with positive interferon-gamma release assays or HIV, but no evidence of tuberculosis disease, could be enrolled if they were ages 5–17. In total, 922 children were randomized in this study to receive daily oral levofloxacin or placebo for 24 weeks. Both studies showed numerical decreases in the incidence of tuberculosis, with a tuberculosis incidence of 0.6% in the levofloxacin group versus 1.1% in the control group at 30 months in VQUIN and an incidence of 1.1% in the levofloxacin group versus 2.6% in the control group at 48 weeks in TB-CHAMP. Neither of these primary outcomes was statistically significant, as both studies were underpowered due to lower-than-expected incidences of MDR tuberculosis in household contacts. A preplanned meta-analysis using individual participant data from the two trials found a 60% relative reduction in tuberculosis incidence among adult and child household contacts of patients with MDR tuberculosis; however, there was an increased risk of musculoskeletal events among participants aged 10 and older [23].

Everything Is Tuberculosis: The History and Persistence of Our Deadliest Infection is an unusual entry in this year's article [24]. This book of nonfiction, written by well-known fiction author John Green, spent 5 months on the New York Times bestseller list. It tells the story of tuberculosis through history, its impact on culture, and the impact culture has had on the treatment and management of this deadly disease. As infectious diseases and public health research and clinical care become increasingly under attack, advocates like John Green are invaluable in inspiring support and commitment to fight against infections.

CONCLUSION

The field of infectious diseases continues to rise to the challenge of solving new problems and improving the care of patients through clinical research. Infections continue to be one of the biggest drivers of morbidity and mortality worldwide, highlighting the ongoing need for the existence of public health and infectious diseases clinical science, as demonstrated in these studies. In 2025, researchers in ID clinical science used technology to improve access and antimicrobial stewardship, discovered new treatment approaches, and prevented infections through innovative vaccination strategies, leading the way for successful interventions in the future.