Issue: Newsletter 4 | September 1, 2025

Randomised Controlled Trials

Antibiotic Use

Zhu L, Zeng X, Shi Y, Wu Y, Zhang X, Xu S, et al. Effectiveness, safety, and pharmacokinetics of linezolid in pediatric bacterial central nervous system infections. J Infect Dis. 2025 Aug 15;232(2):430-440. doi:10.1093/infdis/jiaf169

• Summary: This prospective two-center study in children with gram-positive CNS infections found that linezolid achieved high clinical response (91.1%) and comparable cure rates to vancomycin, showed predictable plasma–CSF pharmacokinetics influenced mainly by body weight, and although associated with more gastrointestinal and hematologic adverse events—particularly at plasma trough levels >7 µg/mL—remained generally well tolerated without treatment discontinuations.
  

Roberts JA, Ulldemolins M, Liu X, et al. Meropenem and piperacillin/tazobactam optimised dosing regimens for critically ill patients receiving renal replacement therapy. Intensive Care Med. 2025 Aug 13. doi:10.1007/s00134-025-08067-w

• Summary: This multinational pharmacokinetic study of 300 critically ill patients on various forms of renal replacement therapy found that dosing requirements for meropenem and piperacillin/tazobactam depend on RRT intensity, duration, and urine output, and showed that extended or continuous infusions achieve effective antibiotic concentrations more reliably and with lower daily doses than short infusions, leading to practical dosing nomograms for clinical use.
  

Mukae H, Iwanaga N, Horita N, Komiya K, Maruyama T, Shindo Y, et al. The JRS guideline for the management of pneumonia in adults 2024. Respir Investig. 2025;63(5):811–828. doi:10.1016/j.resinv.2025.06.014

• Summary: The 2024 Japanese Respiratory Society Adult Pneumonia Guidelines emphasize managing pneumonia in Japan’s super-aged population, highlighting the prevention and comprehensive care of older adults, including vaccination, rehabilitation, oral care, and maintaining physical function, while stressing judicious antibiotic use for Nursing and Healthcare-Associated Pneumonia (NHCAP) with stricter antimicrobial stewardship despite retaining the Japan-specific NHCAP category; the guidelines also recommend background assessments and palliative care considerations for recurrent aspiration pneumonia or terminal patients, underscoring the role of advanced care planning and interdisciplinary collaboration in improving prognosis and aligning treatment with patient values.
  

Pogue JM, Harrington J, Wangchinda W, Kaye KS. New perspectives on antimicrobial agents: sulbactam-durlobactam. Antimicrob Chemother. 2025 Aug 22. doi:10.1128/aac.01086-24

• Summary: This article discusses Carbapenem-resistant Acinetobacter baumannii (CRAB) infections, highlighting their global health threat and poor outcomes, and focuses on sulbactam-durlobactam, which was FDA-approved in 2023 for hospital- and ventilator-associated pneumonia caused by susceptible A. baumannii and is now recommended by the IDSA in combination with a carbapenem as the preferred therapy for CRAB; it reviews the preclinical and clinical evidence supporting its use and explores ongoing questions, including whether carbapenem combination is always necessary and potential applications of durlobactam beyond A. baumannii. 

Musher DM. Amoxicillin vs. ceftriaxone to treat pneumonia caused by amoxicillin-non-susceptible Streptococcus pneumoniae. Antimicrob Chemother. 2025 Aug 13. doi:10.1128/aac.00780-25

• Summary: This article comments on a study comparing ceftriaxone and amoxicillin for pneumococcal pneumonia with high MIC (>2 mg/L), noting that while the original study suggested ceftriaxone is significantly more effective, much of the observed difference may actually be attributable to differences in amoxicillin dosing, administration route, and frequency, rather than intrinsic superiority of ceftriaxone.
  

Isler B, Welyczko Z, Jorgensen N, Davis J, Paterson DL. Advancing the management of prosthetic joint infections: a review of randomized controlled trials and emerging evidence. Antimicrob Chemother. 2025 Aug 14. doi:10.1128/aac.00338-25

• Summary: This article reviews recent and ongoing randomized controlled trials (RCTs) on prosthetic joint infection (PJI) prevention and treatment, highlighting that despite established protocols, outcomes remain suboptimal and better strategies are needed, and summarizes advances in three areas: optimization of surgical and antibiotic strategies (including adaptive trials like ROADMAP and SOLARIO), novel therapeutics such as engineered antibacterial peptides, monoclonal antibodies, and new-generation antibiotics targeting biofilms, and prevention strategies, particularly perioperative antibiotic protocols, emphasizing efforts to reduce antibiotic exposure, disrupt biofilms, and improve prophylaxis, with future research suggested to focus on cost-effectiveness, targeted patient subgroups, and combination therapies.
  

Fusetti C, Salari F, Petri F, Rizzo A, Giacomelli A, Cavallo A, et al. High effectiveness of ceftriaxone monotherapy and limited value of routine test-of-cure for gonorrhoea in a low-resistance setting. Clin Infect Dis. 2025 Aug 18;ciaf456. doi:10.1093/cid/ciaf456

• Summary: This article reports that ceftriaxone 1 g monotherapy is highly effective for treating Neisseria gonorrhoeae infections, achieving a 95–97% microbiological cure rate across genital and extragenital sites in a low-resistance setting in Milan, Italy, and finds that most positive test-of-cure (TOC) results were likely due to reinfection or delayed bacterial clearance rather than true resistance, supporting the limited utility of routine TOC and suggesting that targeted follow-up should focus on symptomatic patients or suspected reinfections, while avoiding combination therapy with azithromycin may reduce antibiotic pressure and resistance in other pathogens.
  

Rallet B, Pouy R, Coutureau C, Blot M, Bani-Sadr F, Sixt T, et al. Should we extend the use of oral antibiotics in infective endocarditis? The ENDO-ORAL study. Clin Infect Dis. 2025 Aug 18;ciaf452. doi:10.1093/cid/ciaf452

• Summary: This study evaluated real-world outcomes of switching from intravenous to oral antibiotic therapy in infective endocarditis (IE) and found that, among 333 patients treated in two French tertiary centers from 2016–2023, oral switch therapy showed similar rates of treatment failure (death, recurrence, or need for suppressive therapy) compared to exclusive intravenous therapy, even in patients who would not have met POET trial eligibility criteria, while also increasing days alive outside the hospital, supporting the broader applicability and potential patient-centered benefits of oral therapy in IE management.
  

Ben Shitrit I, Idan D, Hassidim AA, Michael T, Levy A, Pariente G, et al. Doxycycline safety during pregnancy: a large population-based cohort of pregnancies. Infection. 2025 Aug 22. doi:10.1007/s15010-025-02622-9

• Summary: This population-based cohort study of 265,686 pregnancies examined the safety of doxycycline use during pregnancy, including pregnancies ending in stillbirth or termination. Among 2,696 first-trimester exposures, there was no significant increase in major congenital malformations compared with unexposed pregnancies, including organ-specific defects. Third-trimester exposure (n=112) was associated with a higher risk of very-low birthweight, but other late-pregnancy outcomes—such as perinatal mortality, preterm birth, low birthweight, and low Apgar scores—were comparable to unexposed pregnancies. Overall, the study suggests that first-trimester doxycycline use is largely safe, and most late-pregnancy outcomes are not adversely affected, supporting its clinical use when indicated.
  

Shahzad I, Alasmari MS, Zamir A, Rasool MF, Alqahtani F. Clinical pharmacokinetics of metronidazole: a systematic review and meta-analysis. Antimicrob Chemother. 2025 Jul 31. doi:10.1128/aac.01904-24

• Summary: This systematic review and meta-analysis evaluated the pharmacokinetics of metronidazole (MTZ) across diverse patient populations. From 1,882 screened articles, 67 studies met eligibility criteria, and the area under the concentration-time curve (AUC) was analyzed to quantify total drug exposure. Results demonstrated significant variability in MTZ AUC between populations, with substantial heterogeneity across studies. These findings highlight the need for personalized dosing strategies to optimize MTZ’s efficacy and safety in different clinical contexts, supporting evidence-based decision-making in practice.
  

Blumenthal KG, King AJ, Stone VE, Bartels S, Norton DT, Eippert ML, et al. Geospatial socioeconomic indicators and penicillin allergy delabeling in primary care patients. JAMA Netw Open. 2025;8(8):e2528714. doi:10.1001/jamanetworkopen.2025.28714

• Summary: This study analyzed electronic health record data from 76,709 primary care patients at Mass General Brigham and Tufts Medicine and found that only 6.8% of patients with a documented penicillin allergy were delabeled, with delabeling significantly less likely in socioeconomically disadvantaged and more socially vulnerable areas, including those with lower income, higher uninsured rates, and higher unemployment, highlighting inequities in access to evidence-based penicillin allergy evaluation and the potential impact on antibiotic prescribing, antimicrobial resistance, and health outcomes.

Moore H, Yeoh D, Hughes C, Raby E, Sandaradura I. Aminoglycosides: an update on indications, dosing and monitoring. Aust Prescr. 2025;48:133-8. doi:10.18773/austprescr.2025.038

• Summary: The March 2025 update of the Australian Therapeutic Guidelines: Antibiotic reinforces the role of parenteral aminoglycosides—gentamicin, tobramycin, and amikacin—as highly effective first-line empirical therapy for serious Gram-negative infections, highlighting optimized dosing based on lean body weight, the need for therapeutic drug monitoring beyond 48 hours, and the recommendation to use aminoglycosides in combination with another active antimicrobial or source control procedure for non-urinary infections, while noting that monotherapy may be appropriate for urinary tract infections, and emphasizing their continued use to balance efficacy with antimicrobial stewardship amid concerns about toxicity, individualized dosing challenges, and rising resistance from alternative broad-spectrum antibiotics.
  

Vokinger KN, Li G, Wouters OJ. The rise of drug innovation in China—implications for patient access in the United States and globally. N Engl J Med. 2025 Aug 30. doi:10.1056/NEJMp2505821

• Summary: Recent trade and geopolitical tensions between the United States and China have raised concerns about cross-border access to medicines, yet China’s rapid rise in pharmaceutical innovation—reflected in the growing number of new drugs first approved domestically, substantial R&D investment, streamlined regulatory pathways, and development of first-in-class therapies—offers significant opportunities for global patient access, though U.S. regulatory caution, data integrity concerns, and policy measures such as tariffs and proposed restrictions on collaboration highlight challenges, suggesting that enhancing regulatory compliance, fostering FDA–NMPA collaboration, and maintaining stable trade relations could help ensure timely access to promising Chinese-developed therapies while supporting global health and supply-chain resilience.

Phage Therapy

Global AMR R&D Hub. Workshop report: exploring the use of bacteriophages for global health. Berlin, Germany: Global AMR R&D Hub; 2025 Jul 21.

• Summary: This workshop, convened by the Global AMR R&D Hub in Berlin, brought together global experts to assess the role of bacteriophages as a complementary or alternative strategy to antibiotics in tackling antimicrobial resistance, highlighting both their promise and the challenges of clinical evidence, regulation, manufacturing, and equitable access, and concluded with recommendations for inclusive, co-developed approaches that integrate phage therapies into broader AMR and One Health strategies, with particular emphasis on ensuring LMICs are active partners in shaping solutions.
  

Najjar I, De Paula Siqueira C, Nayara Marcelino Santos I, Costa PG, Pereira dos Santos J, Rocha Pereira Junior GF, et al. Phage research in South America: a descriptive overview of trends and gaps. Clin Microbiol Commun. 2025;105135. doi:10.1016/j.cmicom.2025.105135

• Summary: This narrative review mapped bacteriophage research in South America and found that while Brazil, Argentina, Chile, and Colombia lead studies—mostly focused on agriculture and Salmonella in poultry—there are no human clinical trials or case reports despite the region’s high antimicrobial resistance burden, highlighting that although technical capacity exists, regulatory barriers, limited targeting of critically important pathogens, and insufficient public-sector investment hinder clinical translation, underscoring an urgent need for enhanced regional collaboration and investment to advance phage therapy as a viable alternative treatment.

Bacterial Infections

Russell CD, Goeldner-Thompson S, Smith E, Millar JE, Wang B, Parkinson N, et al. Genome-scale meta-analysis of host responses to Staphylococcus aureus identifies pathways for host-directed therapeutic targeting. J Infect Dis. 2025 Aug 15;232(2):e290-e300. doi:10.1093/infdis/jiaf290

• Summary: This meta-analysis of genome-scale studies on host responses to Staphylococcus aureus identified 3867 prioritized host genes, highlighting key cytokine hubs (TLR2, IL-17, IFN-γ, IL-1β), and noncanonical pathways such as autophagy, apoptosis, iron metabolism, and thrombosis, thereby revealing potential therapeutic targets—including platelet-related mechanisms, mTOR-mediated autophagy, BID-mediated apoptosis, and IFN-γ–driven bacterial killing—for improving outcomes in S. aureus infections where conventional antimicrobials are limited.
  

Ziegler MJ, Anesi J, Tolomeo P, Glaser L, Cowden L, Cressman L, et al. Screening and targeted prophylaxis for Clostridioides difficile infection: STOP-CDI. Clin Microbiol Infect. 2025 Aug 12. doi:10.1016/j.cmi.2025.08.004

• Summary: This two-year study of immunocompromised inpatients (solid organ transplant, stem cell transplant, CAR-T, and leukemia treatment) found that the STOP intervention—screening for C. difficile colonization and giving prophylactic enteral vancomycin—significantly reduced hospital-onset C. difficile infection, 90-day CDI, stool output, and length of stay, without increasing VRE infections or mortality.
  

Borgert BJ, Wallen EM, Pham MN. Prostatitis: a review. JAMA. 2025 Aug 11. doi:10.1001/jama.2025.11499

• Summary: Prostatitis, which affects about 9.3% of men, includes acute bacterial prostatitis (usually gram-negative UTIs like E. coli, treated effectively with 2–4 weeks of broad-spectrum antibiotics such as piperacillin-tazobactam, ceftriaxone, or ciprofloxacin), chronic bacterial prostatitis (persistent infection with recurrent UTIs, most often gram-negative, requiring ≥4 weeks of fluoroquinolones like levofloxacin or ciprofloxacin), and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) (pelvic pain ≥3 months with urinary symptoms, diagnosed by exclusion and treated primarily with α-blockers, with only modest benefits seen from anti-inflammatories, pregabalin, or pollen extract).
  

Yusuf S, Carter MJ, Woodruff J, Kalu P, Wormald JCR, Sethu C. Paediatric case of invasive group A streptococcal necrotising myositis: diagnostic challenges and lessons learned. Lancet Infect Dis. 2025 Aug 14. doi:10.1016/S1473-3099(25)00378-0

• Summary: Necrotising myositis, a rare but severe complication of invasive group A streptococcal infection, can present with non-specific early symptoms that may delay recognition, and effective management relies on prompt diagnosis and aggressive surgical intervention, as illustrated in the reported case of a 5-year-old child, highlighting both treatment successes and potential challenges in this life-threatening condition.
  

Spottiswoode N, Neyton LP, Mick E, Kalantar KL, Hao S, Lydon EC, et al. Host-microbe multiomic profiling predicts mortality in sepsis. Am J Respir Crit Care Med. 2025. doi:10.1164/rccm.202410-1996OC

• Summary: In critically ill adults with sepsis, mortality was associated with host factors such as increased neutrophil degranulation gene expression, decreased T cell signaling genes, and elevated interleukin-8, as well as microbial factors including higher microbial mass and dominance, and integrated host–microbe metagenomic and host transcriptomic classifiers predicted sepsis mortality more accurately than the APACHE-III score (AUCs 0.79 and 0.75 vs 0.69), offering new insights into the interplay of host and microbial responses and a novel approach for prognostic prediction in sepsis.
  

Jackson-Litteken CD, Di Venanzio G, Janet-Maitre M, Castro IA, Mackel JJ, Wilson LD, et al. A chronic Acinetobacter baumannii pneumonia model to study long-term virulence factors, antibiotic treatments, and polymicrobial infections. Nat Commun. 2025;16:7617. doi:10.1038/s41467-025-62655-4

• Summary: This study establishes a chronic respiratory infection model of Acinetobacter baumannii in TLR4 mutant mice using low intranasal inoculums that persist for at least three weeks, revealing that the adhesin InvL is a virulence factor critical in later infection stages, enabling evaluation of antibiotic effects on clearance versus persistence, and allowing investigation of polymicrobial interactions—showing that Staphylococcus aureus worsens infection while Klebsiella pneumoniae promotes clearance—thereby addressing limitations of acute models and providing a platform for studying pathogenesis and therapeutics for opportunistic pathogens.
  

Impact of different interventions to stop antimicrobial resistance [Internet]. [cited 2025 Aug 21]. Available from: https://main.ddnw5ncsatbwf.amplifyapp.com/amrscenarios

• Summary: The online chart models the projected economic impact of antimicrobial resistance under five intervention scenarios, showing how each would affect health systems, labor markets, tourism, domestic hospitality, and overall GDP compared with a baseline scenario following historic resistance trends.
  

Parsons JB, Mourad A, Conlon BP, Kielian T, Fowler VG Jr. Methicillin-resistant and susceptible Staphylococcus aureus: tolerance, immune evasion and treatment. Nat Rev Microbiol. 2025 Aug 20. doi:10.1038/s41579-025-01226-2

• Summary: This review highlights that Staphylococcus aureus, including methicillin-resistant strains (MRSA), can infect any organ system and evade both the immune response and all available antibiotics, and despite advances in new antibiotics and high-quality clinical data, it remains a leading cause of bacterial mortality worldwide, with the article summarizing current basic research on host-pathogen-antibiotic interactions as well as updates on contemporary clinical strategies for its treatment and prevention.
  

Liu Z, Tang Y, He M, Xu C. Molecular drivers of fusion plasmid: mechanistic insights and evolutionary implications. J Antimicrob Chemother. 2025 Aug 20;dkaf309. doi:10.1093/jac/dkaf309

• Summary: This review examines how plasmid fusion—where distinct plasmids recombine into a single plasmid—serves as a key evolutionary mechanism that accelerates bacterial adaptation under antibiotic pressure by generating multidrug-resistant megaplasmids, enabling transfer of non-conjugative plasmids, and producing virulence-resistance hybrids, while also outlining the molecular triggers and mechanisms driving this process and proposing a framework to study how fusion plasmids balance genetic redundancies, with the goal of identifying intervention targets to curb their spread.
  

Larkin C, Valappil SP, Palanisamy N. Global prevalence of nitrofurantoin-resistant uropathogenic Escherichia coli (UPEC) in humans: a systematic review and meta-analysis. J Antimicrob Chemother. 2025 Aug 20;dkaf305. doi:10.1093/jac/dkaf305

• Summary: This systematic review and meta-analysis of 63 studies covering 774,499 uropathogenic E. coli (UPEC) isolates from 1996–2024 found a global nitrofurantoin resistance prevalence of 6.9%, with Asia showing the highest rates and Europe the lowest, revealing an increase in resistance from the early 2000s before a slight decline in recent years, and underscoring the urgent need for targeted education and strengthened antimicrobial stewardship—especially in low- and middle-income countries—to curb the rise of antimicrobial resistance.
  

Halim J, Keane AP, Bouzo J, Aderibigbe T, Chicola JA, Nolan KT, Jonnalagadda K, Tran JX, Carabetta VJ. Synergistic cefiderocol-containing antibiotic combinations active against highly drug-resistant Acinetobacter baumannii patient isolates with diverse resistance mechanisms. J Antimicrob Chemother. 2025 Aug 20;dkaf306. doi:10.1093/jac/dkaf306

• Summary: This study tested cefiderocol alone and in combination with 17 antibiotics against extensively and pan-drug-resistant Acinetobacter baumannii clinical isolates, finding that while cefiderocol alone was active against two-thirds of strains, its combinations—particularly with ceftazidime/avibactam and sulbactam/durlobactam—showed consistent and potent in vitro synergy, reduced resistance in NDM-1-producing strains, and highlighted promising therapeutic strategies that merit further clinical evaluation.
  

Deas G, Lee TC, Colston J, Albur M, Vasant J, Nobbs AH, et al. Streptococcal endocarditis: a meta-analysis of species dependant risk. eClinicalMedicine. 2025;87:103425. doi:10.1016/j.eclinm.2025.103425

• Summary: This meta-analysis of 14,183 streptococcal bloodstream infections, including data from four large hospitals, found that the so-called “small five” species—Streptococcus mutans, S. cristatus, S. gordonii, S. gallolyticus, and S. sanguinis—although responsible for only 8% of all streptococcal bacteraemias, account for nearly 40% of streptococcal infective endocarditis (IE) with individual infection risks up to ~50%, while Streptococcus mitis/oralis, the most common IE pathogen overall, carries a lower and heterogeneous IE risk (~12%), suggesting that current guidance assuming uniform risk across streptococcal species may underestimate the high-risk contribution of specific species and that species- or subspecies-level risk stratification warrants further study.
  

van Kempen EB, Tulling AJ, von Asmuth EGJ, van der Aa LB, Bijker EM, Bijlsma M, et al. Risk factors for severe pediatric invasive group A streptococcal disease. JAMA Netw Open. 2025;8(8):e2527717. doi:10.1001/jamanetworkopen.2025.27717

• Summary: This cohort study of 617 children with invasive group A streptococcus (iGAS) in the Netherlands found that severe disease—defined by intensive care admission or death—was associated with post–COVID-19 pandemic diagnoses, pulmonary involvement, streptococcal toxic shock syndrome, meningitis or encephalitis, and clinical signs including reduced consciousness, dyspnea, abnormal auscultation, elevated C-reactive protein, and decreased estimated glomerular filtration rate, with incidence and severity of iGAS rising sharply in the post-pandemic period compared with pre-pandemic levels, highlighting the importance of recognizing these risk factors to identify at-risk children and improve clinical outcomes.
  

Liao CH, Huang YL, Ioerger T, Lim KS, Huang YC, Huang CH, et al. Genomic and phenotypic insights into antibiotic resistance and virulence of Klebsiella pneumoniae from the environment in southern Taiwan. J Infect Dis. 2025 Aug 1. doi:10.1093/infdis/jiaf396

• Summary: This study of 68 Klebsiella pneumoniae isolates from 62 surface water sites in southern Taiwan found that environmental waters frequently harbor genetically diverse strains, including multidrug-resistant (7.35%) and hypervirulent clones (5.88% such as KL1-ST23 and KL2-ST373), many exhibiting virulence traits like serum resistance, biofilm formation, and intestinal adhesion, with some isolates capable of transferring ciprofloxacin resistance, highlighting that surface waters can act as reservoirs for antimicrobial resistance and hypervirulence and underscoring the need for integrated environmental surveillance and One Health strategies to mitigate public health risks.
  

Mossialos E, Essack S, Mackay I, Anderson M. A layered strategy for tackling antimicrobial resistance: the Swiss cheese model for policy, prevention, and engagement. Lancet Microbe. 2025;101215. doi:10.1016/j.lanmic.2025.101215

• Summary: This review applies the Swiss cheese model to antimicrobial resistance (AMR), illustrating how the convergence of failures across human, animal, plant, and environmental health—such as inappropriate antimicrobial use, poor infection prevention and control, and environmental contamination—can drive resistance, and emphasizes that a robust, multitiered response requires coordinated One Health strategies including sanitation, vaccination, stewardship programs, diagnostics, public awareness, food safety, regulation, integrated surveillance, sustained funding, workforce development, and innovation, highlighting that only through multisectoral collaboration and strategic investment can AMR be effectively mitigated and the efficacy of antimicrobials preserved globally.
  

Borel N, Longbottom D, Greub G, Albini S, Vanrompay D, Laroucau K. Zoonotic infections due to avian Chlamydia abortus: what are we missing? Lancet Microbe. 2025;101197. doi:10.1016/j.lanmic.2025.101197

• Summary: This Personal View reviews Chlamydia abortus, an obligate intracellular bacterium primarily affecting ruminants and causing reproductive failures, and its emerging zoonotic risk from both ruminant and avian strains. Ruminant C abortus, historically the agent of ovine enzootic abortion, mainly infects sheep and goats but can also infect other livestock and humans, posing serious risks to pregnant or immunocompromised individuals, including miscarriage and pneumonia. Avian C abortus strains, previously classified as C psittaci/C abortus intermediates, have been linked to community-acquired pneumonia in humans and detected across wild and captive birds worldwide. Challenges in diagnostics, insufficient surveillance, evolving taxonomy, and overlapping nomenclature with C psittaci complicate accurate risk assessment. The review emphasizes the need for a One Health approach, multidisciplinary collaboration, precise strain classification, and targeted surveillance to mitigate zoonotic transmission and improve public health responses.
  

Sharaf S, Lawes T, Roos D, Okoliegbe I, Alapati S, Ribeiro A, et al. Universal versus targeted chlorhexidine and mupirocin decolonisation and clinical and molecular epidemiology of Staphylococcus epidermidis bloodstream infections in patients in intensive care in Scotland, UK: a controlled time-series and longitudinal genotypic study. Lancet Microbe. 2025;6:101118. doi:10.1016/j.lanmic.2025.101118

• Summary: In two Scottish ICUs, de-escalating universal biocide decolonisation to targeted MRSA carrier decolonisation reduced meticillin-resistant Staphylococcus epidermidis bloodstream infections, multidrug-resistant sequence types, and resistance genes without increasing overall bloodstream infections, suggesting that in low-MRSA settings, universal decolonisation may select for invasive MRSE strains.
  
• Editorial:
  Temsah MH, Al-Tawfiq JA. Repopulate, not just decolonise—a microbial ecological strategy against multidrug resistance in intensive care units. Lancet Microbe. 2025;101206. doi:10.1016/j.lanmic.2025.101206
  • Summary: This article discusses a paradigm shift in hospital infection control, highlighting research by Sharaf et al. showing that moving from universal to targeted decolonisation in ICUs reduces meticillin-resistant Staphylococcus epidermidis bloodstream infections, and proposes a three-phase strategy—AI-driven in-silico modelling, in-vitro environmental trials, and in-vivo patient-specific microbiota recolonisation—to restore ecological balance by introducing antibiotic-sensitive commensal microbes, with evidence suggesting that such microbial repopulation, alongside conventional cleaning and antimicrobial stewardship, could prevent multidrug-resistant organism colonisation and infection while avoiding the selective pressures that drive resistance.

Mycobacterial Infections

Horne DJ, Zifodya JS, Shapiro AE, Church EC, Kreniske JS, Kay AW, et al. Xpert MTB/RIF Ultra assay for pulmonary tuberculosis and rifampicin resistance in adults and adolescents. Cochrane Database Syst Rev. 2025 Jul 29;7(7):CD009593. doi:10.1002/14651858.CD009593.pub6

• Summary: This updated Cochrane review found that Xpert MTB/RIF Ultra is a highly accurate WHO-recommended rapid diagnostic test, with pooled sensitivity and specificity of about 91% and 95% for pulmonary tuberculosis and 96% and 98% for rifampicin resistance, respectively, though accuracy was somewhat reduced in people with smear-negative/culture-positive TB, those with prior TB history, and in interpreting trace-positive results; despite limited adolescent data, the review confirms that Xpert Ultra provides rapid, reliable detection that can facilitate timely treatment of rifampicin-resistant and multidrug-resistant tuberculosis.
  

Dahl VN, Wetzstein N. Building on the past: revisiting historical tuberculosis trials in a modern era. Clin Microbiol Infect Commun. 2025 Aug 16. doi:10.1016/j.cmicom.2025.105132

• Summary: This article revisits five landmark clinical trials from 1947 to the 1980s that established today’s standard six-month four-drug regimen for drug-susceptible tuberculosis, highlighting their pivotal role in shaping both TB treatment and modern clinical research while reflecting on their ethical and methodological limitations compared to current standards, and exploring how lessons from the past can inform more inclusive, pragmatic, and ethically rigorous TB trials today.
  

Mackay E, Platt G, Peloquin CA, Brooks MB, Coit JM, Velásquez GE, et al. Impact of pharmacogenetics on pharmacokinetics of first-line antituberculosis drugs in the HIRIF trial. J Infect Dis. 2025;232(2):e258–e265. doi:10.1093/infdis/jiaf195

• Summary: A pharmacogenetic study of 90 participants from the HIRIF trial in Peru found that a single NAT2 tag SNP (rs1495741) accurately predicted isoniazid pharmacokinetics, while a SLCO1B1 SNP (rs4149032) may influence rifampicin exposure, suggesting that simplified genotyping could guide individualized TB drug dosing, though further research is needed to confirm effects across populations.
  

Donovan J, Cresswell FV, Tucker EW, Davis AG, Rohlwink UK, Huynh J, et al. A clinical practice guideline for tuberculous meningitis. Lancet Infect Dis. 2025. doi:10.1016/S1473-3099(25)00364-0

• Summary: The Tuberculous Meningitis International Research Consortium conducted a systematic review across multiple countries to develop evidence-based practice guidance for the diagnosis, anti-tuberculosis therapy, adjunctive anti-inflammatory treatment, and neurocritical care of tuberculous meningitis, providing recommendations while highlighting substantial knowledge gaps and key research priorities.
  

Law S, Fulcher I, Ashraf S, Bastard M, Docteur W, Franke M, et al. Characterizing treatment adherence trajectories in the endTB multisite cohort of drug-resistant tuberculosis patients: an application of group-based trajectory modelling. Clin Infect Dis. 2025 Aug 22;ciaf467. doi:10.1093/cid/ciaf467

• Summary: This study of 1,787 patients with rifampicin- or multidrug-resistant TB used group-based trajectory modelling to uncover four distinct adherence patterns, showing that while consistently low or declining adherence was strongly linked to poor outcomes, patients who improved adherence over time achieved success comparable to those with consistently high adherence—highlighting that adherence trajectories, rather than fixed thresholds, may better predict treatment outcomes and guide patient support strategies.
  

Sinha P, Bhargava M, Dauphinais MR, Carwile ME, Horsburgh CR Jr, Singh UB, et al. In-kind nutritional supplementation for persons with drug-susceptible tuberculosis and their household contacts would be cost-effective for reducing tuberculosis incidence and mortality in Jharkhand, India: a modeling study. Clin Infect Dis. 2025 Aug 20;ciaf400. doi:10.1093/cid/ciaf400

• Summary: This study shows that providing monthly food baskets plus micronutrients to household contacts of TB patients could substantially reduce TB illness and death in India, averting over 11,000 DALYs per 100,000 people, while remaining highly cost-effective from both healthcare and societal perspectives—strongly supporting the integration of nutritional support into TB prevention strategies, especially in resource-limited settings.
  

Elmorsy EM, Alruwaili BDM, Alrwaili HRH, Alrawaili ASJ, Alanazi AMM, Alanazi FNK, et al. Critical care management of tuberculosis: challenges, evidence, and evolving strategies. Anaesth Pain Intensive Care. 2025;29(5):405–417. doi:10.35975/apic.v29i5.2867

• Summary: This review examines the management of tuberculosis in intensive care settings, highlighting that critically ill patients often present with respiratory failure, sepsis, or CNS involvement and face very high mortality rates (30–70%) due to diagnostic delays, altered drug pharmacokinetics, and rising drug resistance, while stressing the importance of early detection, prompt antitubercular therapy, individualized treatment strategies, and multidisciplinary supportive care, and calling for prospective research to establish ICU-specific guidelines, especially for MDR/XDR-TB and co-infections.
  

Poore H, Wambi P, Nkereuwem E, Nakafeero J, Gomez MP, Nsereko M, et al. The three-gene Xpert Host Response signature for pediatric tuberculosis screening: a prospective diagnostic accuracy study. Clin Infect Dis. 2025 Aug 21;ciaf445. doi:10.1093/cid/ciaf445

• Summary: This study evaluated the GeneXpert MTB Host Response (Xpert-HR) blood-based gene signature test in children under 15 years in The Gambia and Uganda, finding that while the test achieved high sensitivity (up to 88.5%) for detecting confirmed TB, its low specificity (around 30%) limits diagnostic accuracy and risks overdiagnosis, particularly in children under 5, with results indicating that improved pediatric-specific gene signatures are needed for more reliable TB screening in this population.
  

Clark RA, McQuaid CF, Richards AS, Bakker R, Sumner T, Prŷs-Jones TO, et al. The potential impact of reductions in international donor funding on tuberculosis in low-income and middle-income countries: a modelling study. Lancet Glob Health. 2025;13(9):e1517-e1524. doi:10.1016/S2214-109X(25)00232-3

• Summary: This study models the potential global impact of reductions in international donor funding—particularly following the 2025 dismantling of USAID and additional cuts from major donors—on tuberculosis (TB) burden in low- and middle-income countries, projecting that termination of USAID funding alone could result in approximately 1.4 million excess TB cases and over 537,000 additional deaths by 2035, with further reductions from The Global Fund and other countries potentially causing millions more cases and deaths, highlighting the critical need for sustained domestic and international financial support to maintain prevention, diagnostic, and treatment services and to continue progress toward WHO’s End TB targets.3
  

Gu AK, Qin WH, Zhang XJ, Ma FK, Zhang LT. Targeted next-generation sequencing for etiologic diagnosis of cutaneous Mycobacterium marinum infection. JAMA Dermatol. 2025 Aug 20. doi:10.1001/jamadermatol.2025.2905

• Summary: This study evaluates the use of targeted next-generation sequencing (tNGS) for diagnosing cutaneous Mycobacterium marinum infection, comparing its sensitivity and specificity against conventional methods—microbial culture, smear microscopy, histopathology—and Sanger sequencing, to assess whether tNGS offers a more accurate and efficient diagnostic approach for cutaneous nontuberculous mycobacterial infections.

Fungal Infections

Reinhold I, Picardi S, Liss B, Seidel D, Stemler J, Koehler P, et al. Towards shorter therapy for candidaemia: defining uncomplicated candidaemia in adults. Lancet Infect Dis. 2025 Aug 20. doi:10.1016/S1473-3099(25)00409-8

• Summary: This review proposes clearer definitions for uncomplicated versus complicated candidaemia, suggesting that uncomplicated cases be defined by controlled infection source, clinical response, and bloodstream clearance within 5 days of appropriate antifungal therapy, while complicated cases involve factors like deep organ involvement, immunocompromise, recurrence, or resistance; the authors argue that shorter treatment durations could be appropriate for uncomplicated cases but require validation in clinical trials.
  

Lou Y, Wang Y, Liu J, Wang YJ, Wang J, Ma S, et al. Voriconazole-induced liver injury: incidence patterns and risk factors in a retrospective cohort. Antimicrob Chemother. 2025 Jul 31. doi:10.1128/aac.00487-25

• Summary: This large cohort study of 7,659 voriconazole-treated adults systematically characterized voriconazole-induced liver injury, showing an incidence of 11.3% with hepatocellular, cholestatic, and mixed patterns, and identified key risk factors including modifiable ones such as intravenous administration and non-modifiable ones such as pre-existing liver disease, diabetes, transplant status, and elevated laboratory markers, leading to the proposal of a risk-stratification framework to guide personalized monitoring and safer antifungal therapy.
  

Hosseini-Moghaddam SM, Fishman JA. Pneumocystis pneumonia in thoracic organ transplantation: current perspectives and updates. JHLT Open. 2025;10:100367. doi:10.1016/j.jhlto.2025.100367

• Summary: This review highlights that Pneumocystis jirovecii pneumonia (PCP) remains a serious opportunistic infection in thoracic solid organ transplant recipients, where diagnosis is often delayed due to nonspecific symptoms but has been improved by molecular tools (qPCR, ddPCR, LAMP) and emerging AI-based imaging, while treatment still relies on TMP-SMX despite toxicity concerns, with alternative regimens and glucocorticoid use remaining uncertain, and underscores the importance of prophylaxis, careful immunosuppression management, and the need for future interventional studies to refine risk stratification, prevention, and evidence-based management strategies.
  

Rutakingirwa MK, Ssebambulidde K, Okurut S, Kwizera R, Nabwana M, Gakuru J, et al. Cerebrospinal fluid mononuclear cell phenotype and activation predictors of 2-week and 1-year survival among persons with HIV-associated cryptococcal meningitis. J Infect Dis. 2025 Aug 21. doi:10.1093/infdis/jiaf449

• Summary: This study investigates immune correlates of survival in HIV-associated cryptococcal meningitis, finding that early mortality within two weeks is associated with low baseline CSF CD8+ T cells, increased PD-1 expression on T cells, and a CD14+ monocyte phenotype characterized by low HLA-DR and high CD163, while longitudinal follow-up shows a significant reduction in CSF cryptococcal antigen titers over one year, with about 38% of patients testing negative, highlighting the roles of immune exhaustion and macrophage activation in early outcomes and treatment response.
  

Song Y, Buil JB, Rhodes J, Zoll J, Tehupeiory-Kooreman M, Ergün M, et al. Triazole-resistant Aspergillus fumigatus in the Netherlands between 1994 and 2022: a genomic and phenotypic study. Lancet Microbe. 2025;6:101114. doi:10.1016/j.lanmic.2025.101114

• Summary: This study analyzes 29 years of clinical Aspergillus fumigatus isolates in the Netherlands, finding that 15.6% harbored cyp51A-mediated triazole resistance—primarily TR34/Leu98His and TR46/Tyr121Phe/Thr289Ala variants—with 17.2% of resistant isolates showing genotype and phenotype variation, and reports that mixed-genotype infections in triazole-resistant invasive aspergillosis complicate clinical management, often requiring multiple antifungal treatment switches, highlighting the limitations of current molecular diagnostics and the urgent need for improved detection methods to guide therapy.

Diagnostics

Ravi C, Irwin AD, Harris PNA. Probe-capture targeted next-generation sequencing: A novel approach for pathogen and antimicrobial resistance detection in sepsis. Clin Transl Discov. 2025 Aug 13. doi:10.1002/ctd2.70079

• Summary: This article is about improving the diagnosis of sepsis caused by bloodstream infections by comparing conventional blood cultures with advanced sequencing methods, specifically metagenomic next-generation sequencing (mNGS) and probe-capture targeted NGS (tNGS), showing that probe-capture tNGS can detect pathogens and antimicrobial resistance genes faster and more sensitively than traditional methods, enabling earlier, targeted treatment, while also discussing the technical, practical, and cost challenges that must be addressed before it can be widely implemented in clinical practice.

Do Van Dong, Le Thi Kieu Linh, Nguyen Thi Tuyet Nga, Nghiem Xuan Hoan, Nguyen Thi Khanh Linh, Tran Thi Thanh Huyen, et al. Evaluating the diagnostic utility of 16S Oxford Nanopore Technology sequencing in patients with central nervous system infections and its usefulness in antimicrobial stewardship. J Infect Dis. 2025;232(2):e309–e317. doi:10.1093/infdis/jiaf280

• Summary: This study demonstrates that untargeted 16S rRNA Oxford Nanopore Technology (ONT) sequencing of cerebrospinal fluid outperforms conventional culture in detecting bacterial and fungal pathogens in central nervous system infections, identifying additional pathogens missed by culture and revealing that 61% of patients received inappropriate empirical antibiotics, highlighting the potential of 16S ONT to improve diagnostic accuracy, guide targeted therapy, and enhance antimicrobial stewardship, especially in resource-limited settings.
  

Sambri V, Agnoletti V, Ambretti S, Bartoletti M, Bernaschi P, Bignami EG, et al. The role of rapid and advanced microbiological methods in critical care: 2025 EMANUELE RUSSO Delphi Consensus. Clin Microbiol Infect. 2025 Aug 28. doi:10.1016/j.cmi.2025.08.022

• Summary: This study presents a Delphi consensus from a multidisciplinary expert panel providing guidance on the use of rapid and advanced microbiological techniques in critically ill patients, emphasizing that results must be interpreted within specific clinical contexts, that standard culture testing should run concurrently, and that turnaround times under 24 hours are clinically valuable, particularly in severe infections such as sepsis and ventilator-associated pneumonia, while also highlighting the need for clinical bioinformatics expertise, basic clinician training, and further standardization and cost-effectiveness evaluation of these advanced diagnostics.

Improving Clinical Trials

Liu S, Guo B, Thompson L, Nie L, Yuan Y. Is repeated Bayesian interim analysis consequence-free? arXiv. 2025 Aug 10; arXiv:2508.07403. doi:10.48550/arXiv.2508.07403

• Summary: This article shows that repeated Bayesian interim analyses, if conducted without proper multiplicity adjustment, can substantially distort key trial properties such as bias, error rates, coverage, and power, and through theoretical justification and extensive simulations across different trial designs and prior specifications, it emphasizes the need for careful adjustment, prior selection, and evaluation to maintain valid and reliable inference in Bayesian adaptive clinical trials.
  

Menyhárt O, Győrffy B. Multiplicity corrections in life sciences: challenges and consequences. Int J Epidemiol. 2025 Aug;54(4):dyaf098. doi:10.1093/ije/dyaf098

• Summary: This introduction highlights the reproducibility crisis in life sciences, emphasizing how complex study designs, multiple comparisons, and pressures to publish inflate false-positive findings, with examples such as the Reproducibility Project: Cancer Biology showing large effect size reductions in replications; it stresses that inadequate adjustments for multiplicity in clinical and epidemiological research undermine reliability, waste resources, and cause trial failures, and sets the stage for proposing solutions to improve statistical rigor and reproducibility.
  

LaLonde A, Nissen SE. Multiplicity control in clinical trials. NEJM Evid. 2025 Jul 22;4(8). doi:10.1056/EVIDctw2400393

• Summary: This review explains how testing multiple hypotheses in a study increases the risk of false discoveries (type I errors), introduces nonstatisticians to standard methods for controlling this error such as Bonferroni and related adjustments, and provides an accessible overview of the graphical testing approach, a structured yet flexible framework that allows researchers to allocate and reallocate error rates across hypotheses while maintaining overall control of type I error.
  

Decker SRR, Serpa Neto A. Bringing credibility to observational research in critical care: the case of target trial emulation designs. Crit Care Sci. 2025 Aug 8;37:e20250142. doi:10.62675/2965-2774.20250142

• Summary: This article contrasts the traditional view that causal inference should rely solely on randomized clinical trials—the gold standard but often impractical or unrepresentative in critical care—with the growing recognition that observational studies, when analyzed with rigorous statistical methods and large real-world datasets, can provide valid causal insights; it highlights how the target trial emulation framework developed by Hernán and Robins has formalized this process by structuring observational analyses to mimic randomized trials, leading to broader acceptance of causal conclusions from observational research in high-impact journals.
  

Fandino W, Dodd M, Kunst G, Law T. Efficient statistical analysis of trial designs: win ratio and related approaches for composite outcomes. Perioper Med. 2025;14:70. doi:10.1186/s13741-025-00550-8

• Summary: This narrative review discusses the limitations of composite outcomes in randomized clinical trials—particularly when mortality is combined with less critical endpoints—and introduces the win ratio (WR) as an alternative method that prioritizes clinically important outcomes like death over less significant events, highlighting its growing use in cardiovascular research and proposing its potential value for perioperative and periprocedural studies, while stressing the importance of understanding both its advantages and limitations to ensure proper application.
  

Hill JA, Pergam SA, Halasa NB, Kumar D, Baden LR, Boeckh MJ. A network for advancing prevention and treatment of infections among immunocompromised individuals. JAMA Netw Open. 2025;8(8):e2528383. doi:10.1001/jamanetworkopen.2025.28383

• Summary: This article highlights the critical need for a dedicated US-based clinical trial network to study therapies and preventive strategies for infectious diseases in immunocompromised individuals—a rapidly growing and high-risk population—emphasizing that current evidence is limited, and proposing a multipronged approach involving public-private partnerships, collaboration with regulatory and funding agencies, and coordinated research infrastructure to generate evidence-based guidance that can improve patient outcomes and public health.
  

Teuwen LA, Gyawali B. Inferior control arms in oncology trials in LMICs: contextualised or compromised? BMJ Oncol. 2025 Aug 25;4(1). doi:10.1136/bmjonc-2025-000931

• Summary: This article critically examines the ethical and scientific concerns of using suboptimal or inferior control arms in cancer drug randomized controlled trials, highlighting that while some trials in middle-income countries may meet local minimum standards, employing inferior comparators undermines the validity and generalizability of results, risks patient harm, and raises issues of research exploitation, emphasizing that control arms should reflect the best proven therapy regardless of trial location and that LMIC participation should focus on context-relevant studies that meaningfully improve patient access and outcomes.
  

Siddique J, Boscardin WJ. Pragmatic prediction models—moving from development to implementation. NEJM Evid. 2025 Aug 26;4(9). doi:10.1056/EVIDe2500195

• Summary: This article highlights that while clinical research has produced hundreds of diagnostic and prognostic prediction models across diseases such as COVID-19, chronic obstructive pulmonary disease, and cardiovascular disease, the majority are never implemented in practice due to both methodological shortcomings and a lack of focus on real-world applicability during model development.
  

Harris PA, Cheng AC. Participants as partners in decentralized clinical trials. NEJM Evid. 2025 Jul 9;4(9). doi:10.1056/EVIDctw2500188

• Summary: This article discusses the advantages and challenges of decentralized clinical trials (DCTs), emphasizing that conducting trial activities outside traditional clinical settings can improve convenience and equitable access, but requires intentional strategies for recruitment, retention, and participant engagement, while highlighting technical, procedural, and participant-centered considerations to optimize DCT implementation, foster trust, and accelerate scientific discovery.

Improving Clinical Trials

Hassoun-Kheir N, Roncal Redin M, Labi AK, Loftus M, Stewardson AJ, Harbarth S, et al. Nomenclature, definitions, and methodological approaches to estimate the association between antimicrobial treatment and clinical outcomes of drug-resistant bloodstream infections: a systematic review. Clin Microbiol Infect. 2025 Aug 6. doi:10.1016/j.cmi.2025.07.033

• Summary: This systematic review reveals substantial heterogeneity and high risk of bias in studies assessing the impact of inappropriate initial antibiotic treatment for drug-resistant bloodstream infections, underscoring the urgent need for harmonized definitions and improved research methodologies.
  

Seitz KP, Casey JD, Semler MW. Patient, treatment, outcome—large simple trials of common therapies. JAMA. 2025;334(5):395-7. doi:10.1001/jama.2025.9657

• Summary: This editorial highlights the need for large, simple randomized trials of common therapies in critical care—using oxygen therapy as an example—to generate practical evidence that can directly inform everyday clinical decisions.
  

Chan AW, Boutron I, Hopewell S, Moher D, Schulz KF, Collins GS, et al. SPIRIT 2025 statement: updated guideline for protocols of randomized trials. JAMA. 2025;334(5):435-43. doi:10.1001/jama.2025.4486

• Summary: This Special Communication introduces the updated Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2025 statement, which includes substantive and structural changes to incorporate new evidence and emerging perspectives.
  

Taylor RS, Manyara AM, Ross JS, Ciani O. Surrogate end points in trials—SPIRIT and CONSORT extensions. JAMA. 2024;332(16):1340-2. doi:10.1001/jama.2024.15219

• Summary: This editorial discusses the use of surrogate endpoints in clinical trials and recent updates to SPIRIT and CONSORT guidelines to improve their design and reporting.
  

Powers JH 3rd, O’Connell RJ. Developing, analyzing, and interpreting outcome assessments to improve endpoints in infectious diseases clinical research. Clin Infect Dis. 2025 Aug 15;81(Suppl 1):S4-10. doi:10.1093/cid/ciaf319

• Summary: This article discusses strategies for developing, analyzing, and interpreting outcome assessments in infectious diseases clinical research, emphasizing the importance of patient-reported outcome measures that capture symptoms, function, and health-related quality of life, and outlines the processes for selecting relevant concepts, ensuring measurement validity, and appropriately analyzing and interpreting results to improve research endpoints and patient care.
  

Howard-Anderson J, Doernberg SB, Dixon D, Gopinath R, Rubin D, Kinamon T, et al. Interagency collaboration for patient-centered antibacterial drug development. Clin Infect Dis. 2025 Aug 15;81(Suppl 1):S11-5. doi:10.1093/cid/ciaf298

• Summary: This article highlights the collaborative efforts of the Antibacterial Resistance Leadership Group and key U.S. agencies to develop and refine patient-centered endpoints, including health-related quality-of-life measures, for registrational antibacterial drug trials—ensuring that research priorities reflect patient experiences, needs, and outcomes.
  

Minter DJ, Wang TW, Rader A, Barton KD, Skalla LA, Boucher HW, et al. A systematic review of health-related quality-of-life measurement in patients with complicated urinary tract infections. Clin Infect Dis. 2025 Aug 15;81(Suppl 1):S16-23. doi:10.1093/cid/ciaf293

• Summary: This systematic review identifies and evaluates measurement tools for health-related quality of life (HRQoL) studied in complicated urinary tract infection patients, revealing a limited but high-quality literature with diverse instruments and highlighting the need for standardization, development, and validation of HRQoL measures that capture patients' experiences for use as trial endpoints.
  

Sutton KN, Lydon E, Rader A, Barton KD, Skalla LA, Wang TW, et al. A systematic review of health-related quality-of-life measurement in patients with acute bacterial skin and skin structure infections. Clin Infect Dis. 2025 Aug 15;81(Suppl 1):S24-31. doi:10.1093/cid/ciaf294

• Summary: This systematic review of health-related quality-of-life (HRQoL) measurement in acute bacterial skin and skin structure infections (ABSSSIs) found that while a wide range of generic and condition-specific instruments have been used, none fully capture the patient experience, with pain and impaired physical functioning being the most commonly affected domains; the findings underscore the need for the development and validation of targeted HRQoL tools for this patient group.
  

Krah NM, Fai C, Sutton KN, Rader A, Barton KD, Skalla LA, et al. A systematic review of health-related quality-of-life measurement in patients with hospital-acquired/ventilator-associated bacterial pneumonia. Clin Infect Dis. 2025 Aug 15;81(Suppl 1):S32-9. doi:10.1093/cid/ciaf296

• Summary: This systematic review found that while existing studies consistently show hospital-acquired and ventilator-associated bacterial pneumonia negatively affects multiple domains of health-related quality of life (HRQoL), there is a lack of standardization and limited research on HRQoL measurement in this patient population, highlighting the need for more robust and uniform assessment tools in future studies.
  

Rader A, Ruffin F, Fai C, Barton KD, Skalla LA, Wang TW, et al. A systematic review of health-related quality-of-life measurement in patients with complicated intraabdominal infections. Clin Infect Dis. 2025 Aug 15;81(Suppl 1):S40-7. doi:10.1093/cid/ciaf299

• Summary: This systematic review identified a wide range of health-related quality-of-life (HRQoL) measures used in studies of complicated intraabdominal infections (cIAIs), finding that while HRQoL generally improves after treatment, symptoms such as pain and fatigue are common and only the diverticulitis quality-of-life instrument has been psychometrically validated in this population, underscoring the need for rigorously tested, disease-specific HRQoL tools for cIAIs.
  

Ruffin F, Sutton KN, Miller J, Lane H, Schexnayder J, Oakes M, et al. A qualitative secondary analysis of patient health-related quality of life in bloodstream infections by source: intra-abdominal, urinary tract, and acute bacterial skin and skin structure infection. Clin Infect Dis. 2025 Aug 15;81(Suppl 1):S48-54. doi:10.1093/cid/ciaf295

• Summary: This qualitative secondary analysis of interview data from patients with bloodstream infections originating from intra-abdominal, urinary tract, or skin/skin structure sources identified six key factors—ranging from preinfection health to fear of recurrence and social support—that shape the impact of these infections on health-related quality of life, illustrating the importance of developing HRQoL measures that reflect patient experiences across different infection types.
  

Robertson DS, Burnett T, Choodari-Oskooei B, Dimairo M, Grayling M, Pallmann P, et al. Confidence intervals for adaptive trial designs I: a methodological review. Stat Med. 2025 Aug 8. doi:10.1002/sim.70174

• Summary: This methodological review—first in a two-part series—examines the challenges of constructing confidence intervals (CIs) for adaptive clinical trial designs, reviews a range of statistical methods for producing valid CIs that account for trial adaptations, and systematically assesses these methods by adaptive design type and desirable CI properties, offering practical guidance for statisticians interpreting results from adaptive trials.
  

Renard Triché L, Jabaudon M, Chevret S. Beyond the ventilator-free days: review of several estimands. Crit Care. 2025;29:343. doi:10.1186/s13054-025-05593-3

• Summary: This review discusses the evolution and application of composite outcomes like ventilator-free days (VFDs) in critical care research, examining various statistical models—including competing risks, multistate, recurrent event, and mixture cure models—for analyzing VFDs, and emphasizes the importance of pre-specifying a suitable estimand and analytic approach tailored to the primary research objective of each study.

General Interest

Peter JV, Venkatesh B, Premkumar PS, Chacko B, Gunasekaran K, Krishna B, et al. Role of adjunctive corticosteroids on clinical outcomes in severe scrub typhus pneumonitis: ASTEROIDS study protocol – a randomised controlled trial. BMJ Open. 2025;15:e104171. doi:10.1136/bmjopen-2025-104171

• Summary: This multicentre randomized controlled trial in India is evaluating whether daily 6 mg dexamethasone improves ventilator-free days, mortality, and respiratory outcomes in 440 patients with severe scrub typhus pneumonitis or ARDS compared with placebo, while also exploring whether antinuclear antibody expression predicts steroid responsiveness, aiming to clarify the role of corticosteroids in this condition.
  

Faheem MSB, Zeeshan N, Atta Ur Rafe S, Samadi S. Bickerstaff encephalitis: a comprehensive narrative review of pathophysiology, clinical features, and global health considerations. Ann Med Surg. 2025;87(8):5122–5131. doi:10.1097/MS9.0000000000003587

• Summary: This narrative review summarizes Bickerstaff brainstem encephalitis (BBE), a rare post-infectious autoimmune neurological disorder related to Guillain–Barré and Miller–Fisher syndromes, highlighting its characteristic ophthalmoplegia, ataxia, altered consciousness, and anti-GQ1b IgG antibodies as key biomarkers, while emphasizing that early recognition and immunotherapy with intravenous immunoglobulin or plasmapheresis improve outcomes, although further research is needed to standardize diagnosis and treatment.
  

Davis JM, Green E, Solomon DA. A blurry line: navigating treatment decisions when the guidelines don’t fit. Clin Infect Dis. 2025 Aug 14;ciaf396. doi:10.1093/cid/ciaf396

• Summary: This case report details a 45-year-old woman with secondary syphilis complicated by ocular and otic involvement, initially presenting with discordant HIV test results, lymphadenopathy, rash including the palms, and splenomegaly, emphasizing the diagnostic challenge, the critical importance of rapid recognition and initiation of parenteral penicillin therapy to prevent irreversible visual and auditory damage, and the need for dynamic, patient-centered management plans that account for structural barriers such as childcare when delivering first-line therapy.
  

Jones DW, Ferdinand KC, Taler SJ, Johnson HM, Shimbo D, Abdalla M, et al. 2025 AHA/ACC/AANP/AAPA/ABC/ACCP/ACPM/AGS/AMA/ASPC/NMA/PCNA/SGIM guideline for the prevention, detection, evaluation and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Hypertension. 2025 Aug 14. doi:10.1161/HYP.0000000000000249

• Summary: This article summarizes the 2025 update of evidence-based guidelines for adult hypertension management, incorporating a comprehensive literature review from 2015–2024 across multiple databases to evaluate prevention, detection, evaluation, and treatment strategies, emphasizing risk stratification, blood pressure measurement standards, lifestyle interventions, pharmacologic therapy recommendations, and implementation of a dynamic, living guideline to support primary care and specialty clinicians in optimizing patient outcomes.
  

Arias CA. In memoriam: George L. Drusano. Antimicrob Chemother. 2025 Aug 19. doi:10.1128/aac.01045-25

• Summary: George L. Drusano, MD, a pioneering figure in antimicrobial pharmacokinetics and pharmacodynamics at the University of Florida, passed away on June 10, 2025, and is remembered for his groundbreaking research elucidating how antibiotics kill pathogens and prevent resistance, his contributions to Antimicrobial Agents and Chemotherapy, and his enduring curiosity, humor, and dedication to translational science that improved patient care.
  

Corrao K, Umpierrez A, Treml A, Szabo A, Michaelis L, Runaas L, et al. 40 is the new 50: reducing the need for platelet transfusions prior to lumbar puncture in adults with hematologic malignancies. Haematologica. 2025;110(8):1845–1848. doi:10.3324/haematol.2023.284321

• Summary: A retrospective study at Froedtert and the Medical College of Wisconsin evaluated the safety of lowering the pre-lumbar puncture (LP) platelet transfusion threshold from 50×10³/μL to 40×10³/μL in adult oncology patients, finding that this policy change significantly reduced platelet transfusions per procedure without increasing the incidence of traumatic taps (46.3% vs. 47.4%) or serious hemorrhagic complications, with only four hematomas observed, two of which occurred in patients receiving tyrosine kinase inhibitors, suggesting that a pre-LP platelet count of 40×10³/μL is generally safe but that additional studies are needed to clarify the impact of low platelet counts on bleeding risk.
  

Schwaber MJ. Lessons I learned from our soldier. Clin Infect Dis. 2025 Aug 14;ciaf433. doi:10.1093/cid/ciaf433

• Summary: This deeply moving account tells the story of a soldier who survived 417 days in the ICU after being shot 13 times, enduring multiple amputations, repeated septic shocks, multi-organ failure, and a host of life-threatening complications, all while demonstrating extraordinary resilience, spirit, and determination; his care required unprecedented medical expertise, collaboration among an entire hospital team, and unwavering support from family, friends, and the community, highlighting not only the marvels of intensive care medicine but also the profound lessons about human strength, hope, and the privilege of witnessing courage and love at the bedside.
  

Zhang JA, Nizet V. The central importance of vaccines to mitigate the threat of antibiotic-resistant bacterial pathogens. Vaccines. 2025;13(9):893. doi:10.3390/vaccines13090893

• Summary: This review highlights that while antibiotics have historically reduced infectious disease burden, the rapid rise of antimicrobial resistance (AMR)—responsible for nearly 5 million deaths in 2023—threatens these gains, and emphasizes that vaccines, by preventing infections, reducing antibiotic use, interrupting transmission of resistant strains, and providing long-lasting and herd-protective immunity without inducing resistance, represent a powerful yet underutilized strategy to mitigate AMR, with current research focusing on vaccines against key multidrug-resistant bacterial pathogens.
  

Sriram A, Kernan KF, Qin Y, Aldewereld Z, Walton AH, Cabler S, et al. Epstein-Barr virus seropositivity, immune dysregulation, and mortality in pediatric sepsis. JAMA Netw Open. 2025;8(8):e2527487. doi:10.1001/jamanetworkopen.2025.27487

• Summary: This cohort study of 320 children with sepsis found that Epstein-Barr virus (EBV) seropositivity is causally associated with immune dysregulation—including elevated inflammatory biomarkers, macrophage activation syndrome, and impaired immune responses—and significantly increases mortality, suggesting that latent EBV infection may contribute not only to chronic immune disorders but also to acute immune dysregulation in sepsis, highlighting a potential public health concern that warrants further investigation.
  
• Commentary:
  Admon AJ, Carlton EF. Causal discovery in sepsis—a (random) walk in the park? JAMA Netw Open. 2025;8(8):e2527496. doi:10.1001/jamanetworkopen.2025.27496
  • Summary: This commentary highlights the study by Sriram et al., which used advanced computational causal discovery methods to demonstrate that Epstein-Barr virus (EBV) seropositivity in children with sepsis is plausibly linked to mortality through both direct effects and indirect pathways involving hyperferritinemia and macrophage activation syndrome, supporting the role of immune dysregulation as a key driver of poor outcomes; the findings emphasize that EBV status is easily measurable, may represent an actionable upstream target, and illustrate how high-dimensional data and causal modeling can help identify mechanistic pathways, refine sepsis phenotypes, and guide precision interventions, although further validation in larger cohorts and integration with clinical expertise is required.
    

Ostermann M, Forni LG, Joannidis M. State of the art: renal recovery after AKI—from basic science to clinical practice. Intensive Care Med. 2025;51:1490–1507. doi:10.1007/s00134-025-08035-4

• Summary: This review summarizes current understanding of acute kidney injury (AKI) recovery in critically ill patients, highlighting that renal repair is an active process where mild injury may allow full regeneration, but extensive damage leads to fibrosis and long-term chronic kidney disease, that recovery is impaired by nephrotoxic exposures, dialysis-related trauma, age, and injury severity, and that post-discharge follow-up and interventions remain inconsistent, emphasizing the urgent need for strategies to promote renal recovery and reduce mortality and long-term complications.
  

Hess F, Baki E, McGinnis J, Wiltgen T, Scholz H, Bernkopf K, et al. Differentiating central fever from infectious fever in intracerebral haemorrhage. Stroke Vasc Neurol. 2025:svn-2025-004441. doi:10.1136/svn-2025-004441

• Summary: This study of 547 intracerebral hemorrhage patients identifies clinical, laboratory, and radiological factors distinguishing central fever from infectious fever, finding that central fever occurs earlier, is associated with higher stroke severity and worse outcomes, and is independently predicted by left hypothalamic involvement, whereas infectious fever correlates with elevated inflammatory markers, highlighting that early onset and hypothalamic lesions can guide evidence-based management of post-ICH fever.
  

Anderer S. Walking 7000 steps a day linked to lower disease and death risk. JAMA. 2025 Aug 15. doi:10.1001/jama.2025.11002

• Summary: A recent meta-analysis of 31 studies in The Lancet Public Health suggests that walking 7,000 steps per day—well below the popular 10,000-step target—significantly reduces the risk of all-cause mortality, cardiovascular disease, dementia, falls, type 2 diabetes, cancer mortality, and depressive symptoms, while even 4,000 steps per day confer health benefits, indicating that more attainable step goals can meaningfully improve health outcomes.
  

Li P, Zhao J, Wang J, Zhu S, Wong GWK, Xiao RP, et al. Advancing physician-scientist training in China—challenges, gaps, and future directions. N Engl J Med. 2025 Aug 30. doi:10.1056/NEJMp2503525

• Summary: Amid a global decline in physician-scientists, China provides a case study highlighting common challenges and scalable strategies for integrating clinical practice with research innovation.
  

Ullrich C, Studer Bruengger A, Huber LC. Fever, malaise, and weight loss in a woman with aortic valve replacement. JAMA. 2025 Aug 27. doi:10.1001/jama.2025.13036

• Summary: This case describes a 72-year-old woman with a bioprosthetic aortic valve presenting with prolonged fever, malaise, weight loss, and night sweats following consumption of raw milk in Elba, whose evaluation revealed elevated inflammatory markers, first-degree AV block, a thickened aortic root on echocardiography, negative blood cultures, and markedly elevated Phase I and II IgG and IgM titers for Coxiella burnetii, consistent with chronic Q fever endocarditis.
  

Azoulay E. On the tightrope between life and graft: immunosuppression in critically ill solid organ transplant recipients. Intensive Care Med. 2025 Aug 19. doi:10.1007/s00134-025-08061-2

• Summary: This article reviews the delicate balance of immunosuppression management in critically ill solid organ transplant recipients, emphasizing that while immunosuppressive drugs are essential for long-term graft survival, infection has become the leading cause of death, and temporary suspension—especially during sepsis—may reduce ICU-acquired infections without significantly affecting short-term mortality, though decisions must account for organ type, time post-transplant, infection risk, and individual patient factors, highlighting the ongoing clinical dilemma of protecting the graft while controlling life-threatening infections.
  

Khadra MN, Abdat W, Alawneh M, et al. From initial suspicion to accurate diagnosis: unmasking rabies in a case of suspected Guillain-Barre syndrome. BMC Pediatr. 2025;25:648. doi:10.1186/s12887-025-05994-x

• Summary: This case report describes an 8-year-old boy in Palestine initially misdiagnosed with Guillain-Barre Syndrome due to progressive limb weakness and areflexia, who was later confirmed to have rabies following a stray dog scratch, illustrating that rabies can mimic other neurological disorders and underscoring the critical importance of early recognition and post-exposure prophylaxis in endemic regions, as the disease is almost universally fatal once symptoms appear.
  

Gatt M, Piton G, Poole D. Revisiting the timing of intervention in necrotising pancreatitis. Intensive Care Med. 2025 Aug 21. doi:10.1007/s00134-025-08078-7

• Summary: This article reviews current evidence on the management of acute necrotising pancreatitis (ANP) and infected necrotising pancreatitis (INP), emphasizing that while adequate drainage is beneficial in confirmed infection, early invasive intervention—particularly before fluid collections mature—offers no net benefit and may cause harm, and that contemporary trials (PANTER, TENSION, POINTER) support three key principles: employing a minimally invasive step-up approach, delaying intervention until at least 4 weeks when feasible, and prioritizing the least invasive methods available, as many patients improve with conservative management alone.
  

Kellum JA, Zarbock A. Why interventions to prevent acute kidney injury are needed now and why preventing long-term outcomes will only come later. Intensive Care Med. 2025 Aug 19. doi:10.1007/s00134-025-08080-z

• Summary: Acute kidney injury (AKI) affects tens of millions globally each year and is linked to serious short- and long-term complications, including chronic kidney disease and death. Clinical trials using major adverse kidney events (MAKE) as outcomes require extremely large sample sizes, as these events also occur without AKI. Enrichment strategies with risk factors or biomarkers help but have limitations. Despite challenges in proving long-term benefits, AKI itself is a patient-centered outcome, and preventing it is urgently needed to reduce morbidity and mortality.
  

Kuo B, Li JH. Pharmacologic therapies for type 2 diabetes. NEJM Evid. 2025 Aug 26;4(9). doi:10.1056/EVIDra2400265

• Summary: Type 2 diabetes (T2D) is a growing chronic disorder managed through lifestyle changes and pharmacologic therapies. Newer drugs not only lower blood glucose but also reduce long-term cardiometabolic complications. This review summarizes recent pharmacologic agents, their cardiometabolic benefits, considerations for patient-specific use, and emerging therapies targeting T2D pathogenesis.

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