Issue: Newsletter 9 | November 15, 2025

Randomised Controlled Trials

Antibiotics

Mitri EA, Reynolds GK, Copaescu AM, Cox F, Waldron JL, Peter JG, et al. State-of-the-art review: antibiotic allergy—a multidisciplinary approach to delabeling. Clin Infect Dis. 2025 Oct 15;81(4):e74–e92. doi:10.1093/cid/ciaf401

• Summary: This article reviews the substantial impact of antibiotic allergy labels on appropriate prescribing, highlights the growing role of delabeling erroneous allergy labels while identifying high risk phenotypes within antimicrobial stewardship programs, and describes modern, multidisciplinary practices for optimizing antibiotic allergy assessment and management.
• Companion article:
  Mitri EA, Reynolds GK, Copaescu AM, Cox F, Waldron JL, Peter JG, et al. Executive summary: state-of-the-art review: antibiotic allergy—a multidisciplinary approach to delabeling. Clin Infect Dis. 2025 Oct 15;81(4):693–694. doi:10.1093/cid/ciaf402
  

Fresán D, Sorlí L, Barceló-Vidal J, Rodrigo-Moreno A, Muñoz R, Subirana I, et al. An easy-to-use predictive score for identifying patients at risk of suboptimal linezolid exposure and candidates for therapeutic drug monitoring. Int J Antimicrob Agents. 2025 Nov 4;107661. doi:10.1016/j.ijantimicag.2025.107661

• Summary: This study shows that standard linezolid dosing yields therapeutic plasma levels in only about one-third of patients due to substantial interindividual variability linked to factors such as age, renal and liver function, critical illness, and dose-to-body-weight ratio; it develops and validates a simple predictive score that accurately flags patients at high risk of overexposure (and moderately predicts underexposure), enabling targeted therapeutic drug monitoring to optimize dosing and improve outcomes.
  

Hernández RB, de Cossio Tejido S, Gimeno FP, García-Bustos V, Lletí MS. Legends, dogmas, presumptions, and demystifications in antibiotic therapy. Rev Esp Quimioter. 2025 Oct 24;38:70. doi:10.37201/req/s01.11.2025

• Summary: This article critically examines common misconceptions in antimicrobial therapy—such as the presumed superiority of intravenous over oral antibiotics, the necessity of longer treatment courses, and the greater efficacy of bactericidal over bacteriostatic drugs—highlighting the importance of source control, surgical intervention, and careful consideration of the human microbiome, and advocates for evidence-based re-evaluation of entrenched practices to optimize antibiotic stewardship and combat antimicrobial resistance.

Kenyon C. Alarming prevalence of gonococcal ceftriaxone resistance in Vietnam—role of periodic presumptive antimicrobials? J Infect Dis. 2025 Oct 31;jiaf553. doi:10.1093/infdis/jiaf553

• Summary: This letter discusses the high prevalence of ceftriaxone-resistant Neisseria gonorrhoeae in Vietnam and Cambodia, highlighting that resistance is linked to domestic travel and being a man who has sex with women—patterns likely driven by widespread use of periodic presumptive therapy (PPT) and prophylactic antibiotics among sex workers, as well as doxycycline post-exposure prophylaxis, and calls for future research to evaluate antimicrobial use in key populations and its contribution to resistance.
  

Ravix A, Di Paolo ER, Dao K, Perez MH, Crisinel PA, Buclin T, et al. Piperacillin dosing in pediatric patients and augmented renal clearance: are current guidelines sufficient to achieve therapeutic concentration coverage? J Antimicrob Chemother. 2025 Oct 31;dkaf387. doi:10.1093/jac/dkaf387

• Summary: This study evaluated piperacillin dosing in hospitalized children using a population pharmacokinetic model and found that standard guideline-recommended intermittent infusions risk underdosing, especially in patients with augmented renal clearance, whereas continuous infusions reliably achieve pharmacodynamic targets, highlighting the need to revise pediatric dosing strategies to account for varying renal function and ensure optimal drug efficacy.

Swenson J. How pooled procurement can expand access to novel antibacterial therapeutics globally. J Infect Dis. 2025 Nov 5;jiaf370. doi:10.1093/infdis/jiaf370

• Summary: This qualitative case study examines how an existing global health pooled procurement strategy could be adapted to include novel antibacterial therapeutics—addressing the market failures that push small innovators toward regulatory approval only in select high-income countries and subsequent insolvency—by identifying the factors needed to expand market access to where these drugs are most needed while ensuring sustainable revenues for developers, thereby improving global patient access and strengthening the long term antibacterial pipeline against antimicrobial resistance.

Keck JM, Dare RK, Saccente M, Vyas KS, Thompson RN. Use of aztreonam–avibactam with rapid eravacycline step-down therapy for a tibial septic non-union by NDM-producing Enterobacter cloacae. Antibiotics. 2025 Nov 4;14(11):1109. doi:10.3390/antibiotics14111109

• Summary: This case report describes a severe orthopedic hardware-associated infection caused by NDM-producing Enterobacter cloacae complex (co-infected with Candida parapsilosis) that was resistant to carbapenems, ceftazidime–avibactam, meropenem–vaborbactam, and cefiderocol, but responded rapidly to aztreonam–avibactam plus micafungin; due to outpatient administration barriers, therapy was transitioned to eravacycline with continued clinical improvement and no relapse at eight weeks, underscoring aztreonam–avibactam as a critical option for NDM-related hardware infections and supporting eravacycline as a feasible outpatient step-down.

Montaner M, Montes M, Alajarin F, López-Argüello S, Oliver A, Moya B. Unravelling the triad of penicillin-binding proteins, β-lactamase activity, and mRNA dynamics in Pseudomonas aeruginosa AmpC induction. J Antimicrob Chemother. 2025 Nov 5;dkaf408. doi:10.1093/jac/dkaf408

• Summary: In Pseudomonas aeruginosa, carbapenems/cefoxitin that inhibit PBP4—but not PBP3-binding agents—drive aligned ampC transcription and β-lactamase activity, while LMW-PBP mutants show huge mRNA induction (~7000-fold) but capped activity (~1100-fold), revealing that transcription poorly predicts enzyme levels and that rational β-lactam/inhibitor therapy should integrate PBP binding, transcriptional responses, and enzymatic activity (with full induction likely requiring PBP4 and CreBC).

Smith S, Reilly CW, Stewart J, Ragh T, Muller VJ, Ismail I, et al. Thrice-weekly post-haemodialysis ceftazidime can achieve adequate pre-dialysis concentrations and clinical cure in patients with melioidosis. J Antimicrob Chemother. 2025 Oct 13;dkaf383. doi:10.1093/jac/dkaf383

• Summary: Reviewing 449 melioidosis cases (26 on chronic intermittent haemodialysis), the study found that in CIHD patients a thrice weekly post dialysis ceftazidime regimen of 2 g/2 g/3 g achieved adequate pre dialysis serum levels, no neurotoxicity, and clinical cure—suggesting this dosing as a viable alternative to daily ceftazidime and that therapeutic drug monitoring with clinical breakpoints can support more individualized treatment.

Reinert JP, Quach V, Carroll S. Duration of therapy with amoxicillin/clavulanate for postoperative antimicrobial prophylaxis of fractures of the facial skeleton: a systematic review and meta-analysis. J Oral Maxillofac Surg. 2025 Nov;83(11):1393–1402. doi:10.1016/j.joms.2025.07.009

• Summary: This systematic review and meta-analysis of 12 studies (including 4 RCTs) on amoxicillin–clavulanate prophylaxis for surgically managed facial fractures found no significant difference in perioperative infection rates between short (≤24 hours) and prolonged (>24 hours) regimens, while adverse events (e.g., gastrointestinal symptoms, C. difficile) were more frequent with longer courses but not statistically significant—supporting short-duration prophylaxis as equally effective with potentially better safety.

Beaubien-Souligny W, Thompson Bastin M, Teixeira JP, Cerda J, Connor MJ Jr, Dijanic Zeidman A, et al. Proceedings of the University of Alabama at Birmingham Continuous Renal Replacement Therapy Academy (2023–2024): managing de-escalation of acute renal replacement therapy and optimizing drug dosing during renal replacement therapy transitions. Kidney360. 2025 Oct;6(10):1798–1809. doi:10.34067/KID.0000000951

• Summary: This review from the UAB CRRT Academy outlines best practices for de-escalating acute renal replacement therapy in ICU survivors of severe AKI—emphasizing the high risk transition from continuous to intermittent modalities, the need to individualize timing and strategy based on volume status, vigilance for complications like failed transition and intradialytic hypotension (which worsen mortality and kidney recovery), and meticulous drug dosing (especially antimicrobials) during this vulnerable period in the absence of randomized trial guidance.

Pai MP, Cojutti PG, Gatti M, Rinaldi M, Tonetti T, Siniscalchi A, et al. Keeping the horse with the cart: are we underdosing tazobactam even when using continuous-infusion ceftolozane/tazobactam for effectively preventing resistance development by ESBL-producing Enterobacterales? Antimicrob Agents Chemother. 2025 Oct 29; doi:10.1128/aac.01215-25

• Summary: Analyzing 139 adults on continuous-infusion ceftolozane/tazobactam with TDM, this study found frequent subtherapeutic tazobactam exposure (38.1% with fCss <4 mg/L) despite adequate ceftolozane (only 2.5% <8 mg/L), driven by tazobactam’s faster and highly variable clearance (mean 7.41 L/h; CV 115% with kidney function explaining just 23% of variability), and showed via modeling that standard fixed ratio dosing yields only 29–54% cumulative response against ESBL-producing Enterobacterales versus 73–82% with higher, optimized regimens—challenging fixed 2:1 formulations and supporting individualized, component guided dosing to maintain efficacy and suppress resistance.

Liljedahl Prytz K, Kryss E, Oxelbark J, Källman J, Nilsson KF, Sundqvist M, et al. β-lactam concentrations monitored in the early phase of community-acquired sepsis in the intensive care unit. J Antimicrob Chemother. 2025 Oct 28;dkaf401. doi:10.1093/jac/dkaf401

• Summary: In a prospective ICU cohort of 50 patients with community-acquired sepsis, serial β-lactam measurements over the first 48 hours showed frequent underexposure (MIC-multiple <1) or overexposure (>8), with lower multiples linked to younger, less comorbid patients and lower creatinine/noradrenaline needs, and higher multiples to elevated creatinine and vasopressor use—supporting early therapeutic drug monitoring and model informed precision dosing to prevent treatment failure and toxicity.

Largiadèr S, Berthod D, Widmer A, Troillet N, Jackson H, Perdrieu C, et al. β-lactam vs non–β-lactam antimicrobial prophylaxis and surgical site infection. JAMA Netw Open. 2025 Oct 31;8(10):e2540809. doi:10.1001/jamanetworkopen.2025.40809

• Summary: Using data from 175 Swiss hospitals and 348,885 eligible surgical patients, this cohort study found that non–β-lactam surgical prophylaxis (1.7% of cases) was associated with significantly higher surgical site infection rates than β-lactams (6.1% vs 2.8%; adjusted odds ratio 1.78, 95% CI 1.59–1.99), with elevated risks seen across procedure types and for specific agents (ciprofloxacin aOR 1.57, vancomycin 1.38, clindamycin 2.12), supporting the need for a RCT to study this.

Sakoh T, Komori K, Harada S, Yamada K, Araoka H. Draft genome sequence of Stenotrophomonas maltophilia strain TUM26315, a bloodstream isolate resistant to cefiderocol and to aztreonam combined with ceftazidime-avibactam. Microbiol Resour Announc. 2025 Oct 30; doi:10.1128/mra.00949-25

• Summary: This report presents the draft genome of Stenotrophomonas maltophilia TUM26315, a genomic group 6 isolate that shows intrinsic resistance to cefiderocol and to aztreonam plus ceftazidime–avibactam despite no prior exposure, and harbors blaL1B and blaL2B β lactamases along with a cirA frameshift mutation.

Chew KL, Cabang JC, Abu Bakar NA, Tan KX, Teo J. Aztreonam–avibactam resistance rates and resistance mechanisms of NDM and NDM/OXA48-like dual-carbapenemase-producing Enterobacterales in Singapore. Pathology. 2025 Dec;57(7):936–940. doi:10.1016/j.pathol.2025.04.010

• Summary: In a collection of 55 NDM and NDM/OXA-48-like dual-carbapenemase–producing Enterobacterales from 46 patients, aztreonam–avibactam resistance was 13.7% overall (with 96.4% essential and 100% categorical agreement between MIC methods), occurring only in E. coli and Providencia rettgeri and driven in E. coli by PBP3 insertions coupled with AmpC (CMY) production—yielding resistance rates of 18.8% across all E. coli, 8.0% in NDM-only E. coli, and 57.1% in NDM/OXA-48 dual E. coli (notably ST361 and ST167, with ST361 dual-CPE isolates closely related), supporting routine aztreonam–avibactam susceptibility testing for invasive NDM-CPE infections.

Boyd SE, Wootton M, Howe RA, Livermore DM, Macgowan AP, Kahlmeter G. Rifampicin as monotherapy for infections caused by Staphylococcus aureus: considerations for not applying ‘breakpoints in brackets’. J Antimicrob Chemother. 2025 Nov 3;dkaf392. doi:10.1093/jac/dkaf392

• Summary: This commentary examines EUCAST’s “breakpoints in brackets” policy and argues that, although rifampicin monotherapy for Staphylococcus aureus is rarely advisable due to rapid emergence of resistance, this reflects resistance risk rather than inherent inefficacy as monotherapy, so rifampicin’s unbracketed breakpoints remain appropriate under EUCAST’s core criterion.

Mauri C, Maraolo AE, Di Bella S, Luzzaro F, Principe L. The revival of aztreonam in combination with avibactam against metallo-β-lactamase-producing Gram-negatives: a systematic review of in vitro studies and clinical cases. Antibiotics (Basel). 2021 Aug 20;10(8):1012. doi:10.3390/antibiotics10081012

• Summary: A systematic review of 35 in vitro and 18 in vivo studies found that the combination of aztreonam with avibactam shows high antimicrobial activity against metallo-β-lactamase (MBL)-producing Gram-negative bacteria—particularly Enterobacterales and Stenotrophomonas—with in vitro susceptibility in 80–85% of isolates, and clinical data from 94 patients (mostly with bloodstream infections) demonstrated 80% clinical resolution and 19% mortality, suggesting this combination is a promising treatment option while awaiting new antimicrobials, though efficacy is limited against MBL-producing Pseudomonas.

Andersson M, Zimmermann N, Kloft C, Aulin LBS. Antibiotic pharmacodynamics: from MIC to advanced metrics and their applications. J Antimicrob Chemother. 2025 Nov 11; doi:10.1093/jac/dkaf374

• Summary: This review highlights the limitations of relying solely on minimum inhibitory concentration (MIC) to guide antibiotic therapy, emphasizes the value of more informative pharmacodynamic (PD) metrics derived from single timepoint or longitudinal data, and advocates for the use of pharmacometric modeling to better understand antibiotic-bacteria interactions and design rational treatments that optimize efficacy and minimize risk in the context of rising multi-drug resistant infections.

Bercot B, Assoumou L, Caméléna F, Voitichouk C, Mérimèche M, Ouattara M, et al. Antimicrobial drug-resistant Neisseria gonorrhoeae infections in men using doxycycline postexposure prophylaxis: a substudy of the ANRS 174 DOXYVAC trial. Clin Infect Dis. 2025 Nov 10; doi:10.1093/cid/ciaf591

• Summary: In the ANRS 174 DOXYVAC trial among MSM on HIV PrEP, doxycycline post-exposure prophylaxis (DoxyPEP) significantly increased high-level tetracycline resistance (35.5% vs. 12.5%) and the prevalence of Neisseria gonorrhoeae isolates with decreased cefixime susceptibility (32.3% vs. 10%) compared with no-PEP, while susceptibility to ceftriaxone, fluoroquinolones, and azithromycin remained unchanged, highlighting the need for close antimicrobial resistance monitoring when implementing DoxyPEP.

Ong SWX, Pinto R, Mahar RK, Rishu A, Davis JS, Fowler RA, et al. Accounting for non-adherence to assigned antibiotic treatment duration for bloodstream infection (BALANCE): a post-hoc analysis of a randomised clinical trial. Lancet Infect Dis. 2025 Nov 11; doi:10.1016/S1473-3099(25)00592-4

• Summary: A post-hoc analysis of the BALANCE trial including 3,581 patients with non-Staphylococcus aureus uncomplicated bloodstream infections found that non-adherence to assigned antibiotic duration (20.3% overall, higher in the 7-day group) was linked to disease severity, infection source, persistent fever or bacteremia, and antimicrobial resistance, but after adjustment using causal inference methods, 7-day antibiotic therapy remained non-inferior to 14-day therapy for 90-day all-cause mortality, supporting 7-day treatment as the standard of care for uncomplicated BSI.

Wangchinda W, Wu JY, Abbo LM, Ackley R, Bartley P, Gilboa M, et al. Effectiveness of imipenem-relebactam for multidrug-resistant Pseudomonas aeruginosa in pneumonia and bloodstream infections in the United States (MIRAGE). Antimicrob Agents Chemother. 2025 Nov 7; doi:10.1128/aac.01325-25

• Summary: The multicenter, retrospective MIRAGE study of 63 critically ill patients with multidrug-resistant Pseudomonas aeruginosa pneumonia or bacteremia found that imipenem-relebactam achieved 56% clinical success at day 30, with 30- and 90-day mortality of 18% and 29%, respectively, while 37% experienced recurrent infections and 39% developed resistance, suggesting that imipenem-relebactam is a viable treatment option for high-risk patients, including those with isolates non-susceptible to other novel β-lactams.

Warecki BA, Moreno DM, Bonomo RA, Vila AJ. Let’s dance: how protein dynamics drive β-lactamase evolution and antibiotic resistance. Biochemistry. 2025 Nov 5; doi:10.1021/acs.biochem.5c00437

• Summary: This perspective discusses how β-lactamases, the primary drivers of β-lactam antibiotic resistance in Gram-negative bacteria, evolve through mutations that shift protein dynamics and favor alternative conformations, enabling gain-of-function adaptations, and highlights how understanding these conformational changes can inform the design of novel allosteric inhibitors to combat antimicrobial resistance.

White BP, Siegrist EA. Carbapenem-resistant Acinetobacter (CRAB) and outpatient antibiotic therapy (OPAT): between a rock and hard place. JAC Antimicrob Resist. 2025 Nov 6;7(6):dlaf201. doi:10.1093/jacamr/dlaf201

• Summary: Treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections, which often require prolonged 6-week courses, is complicated in the outpatient setting due to stability and administration limitations of recommended agents such as sulbactam-durlobactam, ampicillin-sulbactam, and cefiderocol, with complex dosing schedules, limited stability in elastomeric pumps or minibags, and practical barriers for home administration, leaving patients and OPAT programs with suboptimal oral alternatives or challenging regimens, and highlighting the need for extended stability testing, flexible delivery solutions, and updated reimbursement and regulatory strategies to support effective outpatient therapy.

Chen S, Xu M, Yu M, Decherchi S, Hujer A, Bethel C, et al. Binding and unbinding pathways of a β-lactamase inhibitor. ChemRxiv. 2025 Nov 6; doi:10.26434/chemrxiv-2025-x5w5p

• Summary: Using Pseudomonas-derived cephalosporinase-3 as a model, this study elucidates the binding and unbinding dynamics of the boronic acid β-lactamase inhibitor LP06, revealing three distinct binding pathways guided by hydrophobic motifs and a conserved arginine anchor (R349), while hydrogen-bonding interactions can delay productive binding, and comparative analyses across >6,600 serine β-lactamases suggest these mechanistic insights can inform the design of next-generation broad-spectrum β-lactamase inhibitors.
  

Phage Therapy

Tian Z, Gan L, Feng J, Xue G, Du B, Cui J, et al. A capsule-dependent lytic phage for targeting multidrug-resistant and hypervirulent Klebsiella pneumoniae. Appl Environ Microbiol. 2025 Oct 31;e01380-25. doi:10.1128/aem.01380-25

• Summary: This study characterizes phiK2044, a highly specific lytic phage targeting hypervirulent Klebsiella pneumoniae subtypes (including ST23 and capsular K1), demonstrating potent antibacterial activity, broad host compatibility, and safety in mouse models, while identifying the wcaJ gene as essential for phage–host binding, highlighting phiK2044’s dual potential as a therapeutic agent against multidrug-resistant infections and as a model for studying phage–host interactions and capsule-dependent tropism.

Bacterial Infections

Eriksen HD, Porsbo LJ, Bang B, Ank N, Hasman H. New Delhi metallo-β-lactamase-1-producing Klebsiella oxytoca sequence type 2 from toilets as the likely source of nosocomial transmission to patients – a root cause analysis. Infect Prev Pract. 2025 Dec;7:100487. doi:10.1016/j.infpip.2025.100487

• Summary: This study at Aalborg University Hospital investigated the role of hospital bathroom fixtures in spreading NDM-1-producing Klebsiella oxytoca ST2, finding that toilets in specific rooms served as persistent environmental reservoirs harboring distinct genomic sub-clades, and that four patients later became colonized with genetically related isolates, highlighting the critical contribution of bathroom plumbing to nosocomial transmission in the absence of direct patient-to-patient spread.

Neugut YD, Albenberg L, Lewis JD, Neugut AI. Treatment of H pylori in children to prevent gastric cancer. JAMA Pediatr. 2025 Nov 3; doi:10.1001/jamapediatrics.2025.4282

• Summary: Helicobacter pylori infects an estimated 32% of children worldwide, with higher prevalence in low- and middle-income countries, and is associated with gastritis, duodenitis, peptic ulcers, iron deficiency, impaired growth, and gastric cancer—accounting for nearly 90% of global noncardia gastric adenocarcinomas that could potentially be prevented through effective infection control or treatment.

Sartelli M, Coccolini F, Labricciosa FM, Siquini W, Pipitone G, Palmieri M, et al. Personalized approaches to patients with intra-abdominal infections. J Clin Med. 2025 Nov 1;14(21):7774. doi:10.3390/jcm14217774

• Summary: This narrative review outlines a five-factor framework for managing intra-abdominal infections—continuously assessing anatomical extent, infection source, patient clinical status, likely pathogens and resistance patterns, and immune competence—to guide timely source control, PK/PD-informed antimicrobial therapy, and hemodynamic support in critically ill patients.

Armbruster J, Thomas B, Stengel D, Spranger N, Gruetzner PA, Hackl S. Managing nonunions and fracture-related infections—a quarter century of knowledge, and still curious: a narrative review. J Clin Med. 2025 Nov 1;14(21):7767. doi:10.3390/jcm14217767

• Summary: This narrative review synthesizes advances in diagnosing and treating nonunions and fracture-related infections amid rising incidence driven by aging, comorbid patients and multidrug resistance—highlighting the shift from culture-based diagnostics to metagenomic sequencing and advanced imaging, refined orthoplastic strategies for infected open fractures, and local therapy via antibiotic‑loaded bone substitutes—while underscoring the pivotal role of specialized centers and the ongoing need for research, interdisciplinary collaboration, and evidence-based practice to improve outcomes.

Delaunay M, Creveuil C, Dargere S, Isnard C, Saloux E, Fournier A, et al. Assessing the risk of infective endocarditis in Staphylococcus aureus bacteremia: a comparison of 4 scoring systems. Int J Infect Dis. 2025 Nov 2;108183. doi:10.1016/j.ijid.2025.108183

• Summary: In a retrospective cohort of 887 Staphylococcus aureus bacteremia patients, four infective endocarditis risk scores were validated: VIRSTA (and LAUSTAPHEN) achieved 100% sensitivity and NPV, PREDICT D5 and POSITIVE performed slightly less well (sensitivities 92% and 84%; NPVs ~98%), with VIRSTA and POSITIVE showing the highest discrimination (AUC 90.4 and 89.4), but applying these tools would markedly reshape echocardiography use—potentially increasing TEE by up to 389% (VIRSTA) and reducing TTE by 95% (PREDICT D1)—highlighting that despite excellent rule‑out capability, limited specificity risks TEE overuse, warranting case‑by‑case clinical judgment.

Narciso AR, Dookie R, Nannapaneni P, Normark S, Henriques-Normark B. Streptococcus pneumoniae epidemiology, pathogenesis and control. Nat Rev Microbiol. 2025;23:256–271.

• Summary: This review synthesizes recent advances on Streptococcus pneumoniae, noting that while childhood conjugate vaccines have reduced invasive disease in vaccinated children, serotype replacement has driven non‑vaccine types and invasive disease in unvaccinated adults amid rising antibiotic resistance, and highlights new epidemiologic and genomic insights (including COVID‑19 impacts), pathogenesis studies revealing host–virulence factor interactions as therapeutic targets, and promising next‑generation vaccine candidates to inform future prevention and treatment strategies.

Rando E, López-Cortés LE, Rodríguez-Baño J. P2Y12 inhibitors in Staphylococcus aureus bacteraemia: current evidence and clinical implications. Lancet Microbe. 2025 Oct 30;101255. doi:10.1016/j.lanmic.2025.101255

• Summary: This review highlights growing interest in adjunctive P2Y12 inhibitors for Staphylococcus aureus bacteraemia—with preclinical data showing ticagrelor enhances platelet-mediated killing and disrupts S. aureus metabolism, observational clinical studies suggesting ticagrelor may be more protective than clopidogrel (which itself appears beneficial vs no treatment), but evidence to date is limited to non-randomised cardiovascular cohorts, underscoring the need for ongoing randomized trials and for preventive strategies targeting high‑risk populations.

D’Achille G, Cotoloni G, Nunzi I, Brescini L, Fioriti S, Armiento M, et al. Diffusion of OXA-48- and NDM-5-producing Klebsiella pneumoniae ST383 clone in Central Italy. J Antimicrob Chemother. 2025 Nov 3;dkaf397. doi:10.1093/jac/dkaf397

• Summary: This study describes the emergence and clonal spread of dual carbapenemase–producing Klebsiella pneumoniae (OXA-48 and NDM-5) of ST383 in the Marche region of Italy—highly resistant to most antibiotics but susceptible to aztreonam/avibactam (with variable cefiderocol and colistin resistance)—with WGS revealing conserved plasmids carrying blaOXA-48 (Tn1999.2 on IncL) and blaNDM-5 (Tn125-like on IncFIB/IncHI1B or chromosomally integrated), close phylogenetic relatedness consistent with an outbreak and diffusion beyond the index hospital, and international parallels (Italy, UK, Qatar, Egypt) that underscore the mobility of these resistance determinants and the public health need for robust surveillance.

Magnan C, Plumet L, Morsli M, Dunyach-Remy C, Pouget C, Sotto A, et al. A narrative review of coagulase-negative staphylococci in diabetic foot infections. Clin Microbiol Rev. 2025 Nov 4; doi:10.1128/cmr.00121-25

• Summary: This narrative review underscores the growing clinical relevance of coagulase-negative staphylococci in polymicrobial diabetic foot infections—including osteomyelitis—especially after prior antibiotics or with indwelling devices, highlighting their pathogenic mechanisms, frequent antibiotic resistance, and the diagnostic challenge of distinguishing infection from colonization, and recommending clinician recognition of CoNS as true pathogens to guide susceptibility-informed, severity-tailored therapy and strengthen antimicrobial stewardship for better outcomes.

Abdelrahman ST, Kamal NM, Abdelbar SMM, Al Juhmani R, Onyejesi CD, Attalla A, et al. Neonatal sepsis in low-resource emergency settings: evidence-based strategies for early recognition and management. Sage Open Pediatrics. 2025 Oct 29;12. doi:10.1177/30502225251380322

• Summary: This review synthesizes the urgent challenges of neonatal sepsis in low-resource emergency settings—where 99% of cases occur in low- and middle-income countries—highlighting delays from limited cultures, biomarkers, and antibiotic access; compounding factors like antimicrobial resistance, weak infection control, and socioeconomic barriers; and promising, resource-adapted solutions such as point-of-care diagnostics, Kangaroo Mother Care, telemedicine, and AI-enabled tools, calling for affordable diagnostics, judicious antibiotic use, stronger health systems, and international collaboration to reduce mortality.

Hobson CA, Peiffer-Smadja N, Hamard M, Armand-Lefevre L, Birgand G, Kernéis S, et al. Community human-to-human transmission of multidrug resistant Enterobacterales in high-income countries: a systematic review. Clin Microbiol Infect. 2025 Nov 10; doi:10.1016/j.cmicom.2025.105146

• Summary: This systematic review of 105 studies in high-income countries found that community carriage of multidrug-resistant Enterobacterales (MDRE), particularly ESBL-producing strains, has risen from 3.2% in 2002–2009 to 19.3% in 2018–2021, with intra-household transmission affecting 8–37% of contacts, but evidence on effective community-based infection control and antimicrobial stewardship interventions remains limited, highlighting the urgent need for targeted studies to understand and curb MDRE spread outside healthcare settings.
  

Murthy S, Hagedoorn NN, Faigan S, Rathan MD, Marchello CS, Crump JA. Complications and mortality of typhoid fever: an updated global systematic review and meta-analysis. Lancet Infect Dis. 2025 Nov 12; doi:10.1016/S1473-3099(25)00551-1

• Summary: This updated systematic review and meta-analysis of 167 studies found that typhoid fever continues to cause substantial morbidity and mortality, with delirium/confusion being the most common complication (26.5%), typhoid intestinal perforation occurring in 1.7% of cases, an overall case-fatality ratio (CFR) of 2.1% (higher in Africa at 4.7% and the Americas at 2.9% compared with Asia at 1.2%), and a pooled TIP CFR of 16.3%, highlighting the ongoing burden of typhoid and the need for both vaccine and non-vaccine preventive measures.
  

Wei Y, Palacios Araya D, Palmer KL. Enterococcus faecium: evolution, adaptation, pathogenesis and emerging therapeutics. Nat Rev Microbiol. 2024;22:705–721. doi:10.1038/s41579-024-01058-6

• Summary: This review highlights how Enterococcus faecium, including vancomycin-resistant strains, has evolved to colonize humans and animals, survive environmental stresses, resist antibiotics, and persist in clinical settings, offering critical insights into its evolutionary history, adaptation, and dissemination that can inform the development of novel preventive and therapeutic strategies against antibiotic-resistant pathogens.
  

Hayden MK, Sansom SE, Snitkin ES. Genome sequencing for prevention of health-care-associated bacterial infections. Nat Rev Microbiol. 2025 Nov 10; doi:10.1038/s41579-025-01254-y

• Summary: This review discusses how whole-genome sequencing (WGS) can enhance the prevention and control of health-care-associated infections (HAIs) by enabling high-resolution pathogen tracking, predicting antibiotic resistance and virulence, supporting outbreak responses and prospective surveillance, and informing targeted interventions, while emphasizing the integration of genomic, clinical, and epidemiological data and the need for capacity building in low- and middle-income countries to reduce the global HAI burden.

Mycobacterial Infections

Carratalà Castro L, Munguambe S, Kay A, Ssengooba W, Mulengwa D, Acácio S, et al. Estimating the accuracy and additionality of TB-LAM to diagnose TB in children without HIV (AccuLAM). Clin Infect Dis. 2025 Nov 10;ciaf525. doi:10.1093/cid/ciaf525

• Summary: This study addresses the pediatric tuberculosis diagnostic gap by evaluating the urine Determine TB LAM Ag test, finding low sensitivity (15.9%) and moderate specificity (90.6%), with urine collection using an adhesive bag independently associated with markedly higher positivity (odds ratio 11.38), underscoring both limited diagnostic yield and the need to standardize sampling methods.

Bisson GP, Allwood B, Byrne A, Günther G, Khosa C, Navuluri N, et al. Post-tuberculosis lung disease: a case definition for use in research studies. Lancet Infect Dis. 2025 Nov 10; doi:10.1016/S1473-3099(25)00548-1

• Summary: This consensus-driven proposal, developed from the 2nd International Post‑Tuberculosis Symposium and refined by the authors, introduces a harmonised research case definition for post‑tuberculosis lung disease—guided by specificity, feasibility in high‑burden settings, relevance to long‑term outcomes, and applicability across the lifespan—requiring (1) documented prior pulmonary/pleural TB with no active TB at assessment, (2) current evidence of pulmonary disease with abnormalities in at least two of three domains (lung function, respiratory symptoms, chest imaging), and (3) attribution at least in part to prior TB, accompanied by a reporting framework and intended to complement (not replace) study‑specific definitions, with the recognition that it will evolve as outcome data emerge to improve comparability and care for TB survivors.

Inbaraj LR, Srinivasalu VA, Narayanan MK, Bhaskar A, Daniel J, Scandrett K, et al. Diagnostic accuracy of low-complexity, manual nucleic acid amplification tests for the detection of pulmonary and extrapulmonary tuberculosis in adults and adolescents: a systematic review and meta-analysis. Lancet Microbe. 2025 Oct;6(10):101169. doi:10.1016/j.lanmic.2025.101169

• Summary: This systematic review and meta-analysis of 29 studies found that low-complexity TB-LAMP performs well for pulmonary tuberculosis in adolescents and adults (summary sensitivity 84.1% [95% CI 78.3–88.6], specificity 96.1% [94.2–97.4]) and shows promising accuracy for lymph node TB from biopsy tissue (sensitivity 94.3%, specificity 90.0; low-certainty), positioning TB-LAMP as a practical alternative to more infrastructure-intensive molecular tests in resource-limited settings, though it cannot detect rifampicin resistance and needs larger studies for extrapulmonary sites.

Llamas-Lopez A, Seddon JA, Chow FC, Upton CM, Jain SK, Alffenaar JW, et al. Intensified treatment of tuberculous meningitis in adults: a systematic review and meta-analysis. Open Forum Infect Dis. 2025 Oct 7;12(10):ofaf503. doi:10.1093/ofid/ofaf503

• Summary: This systematic review and meta-analysis of 10 adult TB meningitis trials (n=1369) found no significant mortality reduction with intensified regimens—higher-dose rifampicin (OR 0.86, 95% CI 0.54–1.35), adjunctive fluoroquinolones (OR 0.85, 95% CI 0.56–1.27), or linezolid (OR 0.73, 95% CI 0.22–2.43)—with secondary outcomes too heterogeneous to pool, underscoring that current evidence does not support intensified therapy and highlighting the need for uniform case definitions, consistent endpoints (including MRC grading), and standardized dosing in future trials.

Lee-Jones S, Rebe K, Marais S, Meintjes G, Parker A, van der Plas H. Thalidomide as an adjunctive therapy for HIV–tuberculosis–associated immune reconstitution inflammatory syndrome: a case series. Open Forum Infect Dis. 2025 Oct 1;12(11):ofaf617. doi:10.1093/ofid/ofaf617

• Summary: In a case series of seven adults with complicated HIV-associated tuberculosis–IRIS (including CNS TB, adenitis, and recurrent psoas collections) refractory or intolerant to corticosteroids, thalidomide 100 mg daily for 6–12 months was associated with favorable clinical outcomes without adverse effects, suggesting potential utility in this small subset and supporting further studies to refine dosing and duration.

World Health Organization. WHO releases new guidelines on tuberculosis and undernutrition. WHO News. 2025 Oct 8. Available from: https://www.who.int/news/item/08-10-2025-who-releases-new-guidelines-on-tuberculosis-and-undernutrition

• Summary: WHO’s updated TB–undernutrition guidelines (Module 6) elevate people- and household-centred care by recommending routine nutritional assessment and counselling for all people with TB and their household contacts, targeted nutritional interventions for any undernourished person with TB regardless of age, drug resistance or pregnancy, and food assistance to prevent TB among household contacts in food-insecure settings (informed by the RATIONS trial), with implementation supported by an operational handbook and requiring multisector collaboration to integrate nutrition and social support into TB care to improve outcomes and reduce preventable mortality.

Mudde SE, Meliefste HM, Klaassen CHW, Ammerman NC, Pierce JV, Serio AW, et al. Omadacycline as a drug candidate for Mycobacterium avium infections: in vitro insights on single and combination therapies. J Antimicrob Chemother. 2025 Nov 5;dkaf413. doi:10.1093/jac/dkaf413

• Summary: This exploratory in vitro study shows that omadacycline has activity against Mycobacterium avium—affected by medium and drug instability (MIC 128 mg/L in CAMHB vs 8 mg/L in Middlebrook, falling to 1 mg/L with daily supplementation)—exhibits time- and concentration-dependent killing, enhances activity in combinations (most notably with amikacin), and appears to suppress the emergence of amikacin (rrs) and clarithromycin (rrl) resistance, supporting further evaluation of omadacycline, particularly in amikacin-containing regimens, for M. avium disease.

Hughes JA, McMorrow F, Brooks KM, Pinilla M, Fairlie L, Ngocho JS, et al. Pharmacokinetics and safety of clofazimine in women with rifampicin-resistant tuberculosis during pregnancy and the postpartum period: results from IMPAACT P1026s. J Infect Dis. 2025 Oct 30;jiaf504. doi:10.1093/infdis/jiaf504

• Summary: In an observational PK study of 11 pregnant South African women (64% with HIV) treated with clofazimine 100 mg daily for rifampicin-resistant TB, intensive sampling during late pregnancy and 2–8 weeks postpartum showed exposures broadly comparable to nonpregnant RR-TB cohorts but approximately 30% higher in the third trimester than postpartum, with several severe adverse events in mothers and infants deemed unlikely related to clofazimine—suggesting overall similar antepartum/postpartum pharmacokinetics with lower-than-expected postpartum levels.

Yapa HM, MacLean ELH, Menzies NA, Dodd PJ, Dean A, Mirzayev F, et al. Drug-resistant tuberculosis: a priority pathogen for enhanced public health research and practice. Clin Microbiol Rev. 2025 Nov 4; doi:10.1128/cmr.00064-25

• Summary: This narrative review outlines the global burden and setbacks of drug‑resistant tuberculosis—worsened by COVID‑19–related underdiagnosis—highlighting persistent gaps in detection, rapid drug susceptibility testing, and treatment; substantial post‑TB disability (notably chronic lung disease); the promise of shorter, more effective all‑oral MDR‑TB regimens and new antibiotics, advanced therapeutics, and precision medicine; the need for rapid DSTs aligned with new drugs; and a person‑centred, well‑funded, holistic One Health approach to accelerate DR‑TB prevention and care.

Chen X, Cai C, Song L, Lan Y, Yu H, Chen Y, et al. Acquired resistance during short-course treatment for rifampicin-resistant tuberculosis. Clin Microbiol Infect. 2025 Nov 3; doi:10.1016/j.cmi.2025.10.027

• Summary: In a WGS-based analysis nested within China’s TB-TRUST trials of shorter regimens for rifampicin-resistant TB (114 participants with serial isolates), acquired drug resistance occurred in 14.0% (median onset 17 days), most commonly to pyrazinamide (8.6%), followed by bedaquiline (4.5%), ethambutol (4.2%), fluoroquinolones (4.0%), and clofazimine (3.6%), with no ADR to linezolid or cycloserine; ADR was more frequent with poor adherence and was detected in 2 of 13 with bacteriological failure, indicating a non-negligible, early-emerging risk that warrants ongoing surveillance and assessment of clinical impact and regimen potency.

De Lima EL, Aliberti MJR. Childhood tuberculosis and risk of frailty in later life: evidence from a nationally representative study in Brazil. J Infect Dis. 2025 Nov 5; doi:10.1093/infdis/jiaf563

• Summary: Analysis of 8,459 adults in Brazil found that individuals who had tuberculosis in childhood had a significantly higher prevalence of frailty in later life (23.0% vs. 8.8%; prevalence ratio 2.52), with only a small and non-significant mediation effect through chronic obstructive pulmonary disease, highlighting the importance of a life-course approach to TB care.
  

Ghebreyesus TA, Motsoaledi PA. G20 2025: advancing equity and affordability in future tuberculosis vaccines for adolescents and adults. Lancet Infect Dis. 2025 Nov 4; doi:10.1016/S1473-3099(25)00666-8

• Summary: Tuberculosis remains a major global health and socioeconomic burden, particularly affecting people living with HIV and other vulnerable populations, and although existing treatments have saved millions of lives, they are insufficient to meet 2030 SDG targets; new vaccines in advanced clinical trials offer a transformative opportunity to curb transmission, but realizing their potential requires coordinated global action on equitable access, sustainable financing, and rapid deployment, with initiatives such as the WHO TB Vaccine Accelerator Council and the upcoming G20 meeting in Limpopo aiming to ensure that effective vaccines are produced, distributed, and delivered fairly to populations with the highest public health need.

Fungal Infections

Maldonado-Barrueco A, Quiles-Melero I, García-Rodríguez J. Current diagnostic approach to fungal infection in the critically ill patient. Rev Esp Quimioter. 2025 Oct;38(Suppl 1):32–37. doi:10.37201/req/s01.05.2025

• Summary: Invasive fungal infections are an increasing cause of morbidity and mortality in critically ill patients, especially post–SARS-CoV-2, and require a pathogen-specific, integrated diagnostic approach that combines classical methods, biomarkers, and molecular assays to improve detection, guide timely antifungal therapy, and enhance patient outcomes across infections such as candidiasis, aspergillosis, pneumocystosis, and mucormycosis.

Puerta-Alcalde P, Guinea J, Maseda E, Zaragoza R. Review on the management of intra-abdominal candidiasis. Rev Esp Quimioter. 2025 Oct;38:95. doi:10.37201/req/095.2025

• Summary: Intra-abdominal candidiasis, responsible for 10–30% of ICU intra-abdominal infections and associated with prolonged hospitalization and high morbidity and mortality, remains challenging to manage due to uncertainties in microbiological diagnosis, antifungal dosing and peritoneal penetration, and first-line therapy selection, emphasizing that an optimized, multidisciplinary approach integrating rapid diagnostics, tailored antifungal therapy, and effective source control is essential to improve patient outcomes.

Fidanzati A, Scheggi V, Papi M, Stefàno PL. Fungal endocarditis: a retrospective analysis from a high-volume surgical centre and review of the literature. BMC Infect Dis. 2025 Nov 3;25:1479. doi:10.1186/s12879-025-11801-w

• Summary: Fungal endocarditis—a rare (≈2–4%; 1.2% in a 687-patient cohort) but increasingly encountered form of infective endocarditis driven by risk factors like prosthetic valves, indwelling catheters, prolonged fungemia, and injection drug use—remains difficult to diagnose due to nonspecific presentations and often negative/late blood cultures, carries high extracardiac embolic complications and >50% mortality, and requires a high index of suspicion, comprehensive work-up per guidelines, multidisciplinary management, and timely antifungal therapy with early surgery to improve outcomes.

Apostolopoulou A, Kampouri E, Little JS. The changing epidemiology of invasive mold diseases in immunosuppressed patients: what, why, how? Clin Microbiol Infect. 2025 Oct 29; doi:10.1016/j.cmi.2025.10.021

• Summary: This review characterizes the evolving epidemiology of invasive mold diseases by detailing fungal adaptation and emerging antifungal resistance alongside the expanding spectrum of immunocompromised hosts, emphasizing that recognizing these environmental and host-driven shifts is essential for timely diagnosis, management, and informed health policy and research.

Vanbiervliet Y, Aerts R, Maessen L, Wauters J, Maertens J, Lagrou K. Laboratory innovations to diagnose invasive mould infections - what is relevant, what is not? Clin Microbiol Infect. 2025 Oct 29; doi:10.1016/j.cmi.2025.10.017

• Summary: Emerging diagnostics for invasive mould infections—including rapid Aspergillus antigen assays (lateral-flow, chemiluminescent), targeted PCRs for Aspergillus and Mucorales, and selective use of mNGS—enable earlier, more accurate, non-invasive detection, though interpretive and cost barriers persist; multimodal strategies are recommended, host-response assays remain investigational, and prospective multicentre studies are needed to standardize thresholds and validate clinical impact.

Shastri P, Bains G, Henriksen AS, Karas A. Coccidioidomycosis in Europe: a systematic literature review of epidemiology, treatment and outcomes. J Antimicrob Chemother. 2025 Nov 6; doi:10.1093/jac/dkaf407

• Summary: A systematic review of 197 coccidioidomycosis cases reported in Europe between 1948 and 2022 found that most infections were linked to migration or travel from endemic areas, primarily affected the lungs (39%) and CNS (10%), often led to delayed treatment due to misdiagnosis, were most commonly treated with fluconazole or amphotericin B, and had higher mortality and stable disease rates in immunocompromised patients, underscoring the need for clinicians to consider cocci in patients with pneumonia or meningitis symptoms from endemic regions.
  

Schelenz S, Abdolrasouli A, Armstrong-James D, Ashbee HR, Barton R, Bicanic T, et al. British Society for Medical Mycology best practice recommendations for the diagnosis of serious fungal diseases: 2025 update. Lancet Infect Dis. 2025 Nov 10; doi:10.1016/S1473-3099(25)00550-X

• Summary: This updated guidance from the British Society for Medical Mycology highlights advances in diagnosing invasive fungal diseases in the UK, emphasizing non-culture-based tests such as PCR, antigen, antibody, and molecular assays alongside histopathology and radiology, with new recommendations for Pneumocystis PCR, 1,3-β-D-glucan testing, Aspergillus and Candida PCR, pan-fungal DNA sequencing, and expanded therapeutic drug monitoring, while stressing integration of diagnostics with antifungal stewardship, clinical pathways, and quality improvement to optimize care for adults and children with suspected fungal infections.

Diagnostics

Cantón R, Halperin AV. Diagnostic stewardship in sepsis: minding the gap from the microbiology lab to ward. Rev Esp Quimioter. 2025;38(Suppl 1):11–20. doi:10.37201/req/s01.02.2025

• Summary: Sepsis, a life-threatening response to infection, requires prompt diagnosis and targeted antimicrobial therapy, and this article highlights how diagnostic stewardship programs—integrated with antimicrobial stewardship and supported by advanced microbiological techniques—enhance early, precise detection and treatment, underscoring the vital collaboration between microbiology laboratories, clinical teams, and innovative approaches to optimize patient outcomes.

Sanz S, Burillo N, García-Lechuz JM. Syndromic platforms in the management of infection in the critically ill patient: test indication and diagnostic interpretation. Rev Esp Quimioter. 2025 Oct;38(Suppl 1):4. doi:10.37201/req/s01.04.2025

• Summary: Timely and appropriate empirical antibiotic therapy is crucial for survival in critically ill patients, yet 20–30% receive inadequate treatment—often complicated by multidrug-resistant pathogens—leading to higher mortality and adverse effects, and this article discusses the role of rapid diagnostic tools, including syndromic molecular panels, in early pathogen identification to guide optimal therapy in common ICU infections such as ventilator-associated pneumonia and bacteremia.

Khankan N, Rust TJ, Pallotta AM, Bass SN, Ramsey C, Burns B, et al. Impact of rapid pathogen identification of gram-negative anaerobic bacteria from blood cultures on antimicrobial stewardship. Microbiol Spectr. 2025 Oct 31;e02383-25. doi:10.1128/spectrum.02383-25

• Summary: This study shows that implementing direct-from–positive blood culture MALDI-TOF MS for identifying obligate anaerobic gram-negative bacteria markedly shortens the time to pathogen identification and antibiotic de-escalation in bloodstream infections, demonstrating that rapid diagnostic workflows can accelerate targeted therapy, strengthen antimicrobial stewardship, and improve outcomes for patients with anaerobic bacteremia.

Vaugon E, Dien Bard J. Revisiting diagnostics: multiplex infectious disease panels. Clin Microbiol Infect. 2025 Nov 3; doi:10.1016/j.cmi.2025.10.026

• Summary: This commentary reviews comprehensive multiplex PCR “syndromic panels” (≥6 targets) that expedite infectious disease diagnosis and clinical decision-making, outlining the current landscape, implementation challenges (e.g., workflow integration, interpretation, cost, stewardship), and emerging trends likely to shape their future use in healthcare.

Moreira NK, da Silva Collar G, Salvador JC, Mott MP, Marx R, Barth PO, et al. Turbitest: an innovative rapid test for determining in vitro susceptibility to ceftazidime-avibactam plus aztreonam in Enterobacterales. Eur J Clin Microbiol Infect Dis. 2025 Nov 4; doi:10.1007/s10096-025-05329-9

• Summary: This study introduces TurbiTest, a rapid, inexpensive turbidity-based assay (<5 hours) to assess susceptibility of carbapenem-resistant Enterobacterales to aztreonam–avibactam (AZA) and aztreonam plus ceftazidime–avibactam (ATM–CZA), showing high categorical agreement versus broth microdilution (≈96–99% from colonies; ≈98–100% in spiked blood cultures; ≈93–100% in clinical blood cultures) with all isolates susceptible to AZA and ATM–CZA, and highlights the need for interlaboratory validation and broader population testing.

Lee TC, Prosty CJ, Mappin-Kasirer B, McDonald EG. Optimizing use of the (1-3)-β-D-glucan assay for the diagnosis of Pneumocystis jirovecii pneumonia. CMI Commun. 2025 Mar;2(1):105061. doi:10.1016/j.cmicom.2025.105061

• Summary: By combining a PCP clinical prediction rule with a two-tier interpretation of serum β-D-glucan (BDG), this study outlines when BDG is most useful: a negative BDG <80 pg/mL yields NPV ≥95% if the PCP score is ≤4 in HIV or ≤3 without HIV, whereas a positive BDG >400 pg/mL approaches PPV 90–95% only at scores ≥5.5 (HIV) or ≥6.5 (non-HIV); outside these ranges BDG adds little diagnostic value, supporting a pretest probability–guided approach that warrants prospective multicentre validation.

Lin L, Chen Y, Zhou N, Wu Y, Yu Y, Liu J, et al. Clinical evaluation of digital PCR for rapid pathogen detection in suspected bloodstream infections. Br J Hosp Med. 2025 Oct 24;86(10):1-22. doi:10.12968/hmed.2025.0561

• Summary: In a retrospective cohort of 294 suspected bloodstream infection patients, multiplex digital PCR targeting E. coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa vastly outperformed conventional blood culture (41.5% vs 12.2% positivity), achieved near-perfect accuracy versus blood culture plus Sanger sequencing (sensitivity 99.18%, specificity 99.42%; Kappa 0.99), uncovered 86 additional true positives consistent with pathogens from other sites (supporting early detection of occult infections), and showed elevated procalcitonin independently predicted dPCR positivity (AUC 0.656; optimal cut-off 6.11 ng/mL), suggesting dPCR can streamline diagnosis and treatment for BSI.

Ergan B, Akıllı FM, İlki A. Direct MALDI-TOF MS identification and EUCAST RAST from positive blood cultures: impact on turnaround time in bloodstream infections. Eur J Clin Microbiol Infect Dis. 2025 Nov 7; doi:10.1007/s10096-025-05345-9

• Summary: This study demonstrated that rapid identification (ID) using MALDI-TOF MS directly from positive blood cultures, combined with rapid antimicrobial susceptibility testing (RAST) following EUCAST criteria, achieved high accuracy for most bacterial groups and progressively readable inhibition zones, with categorical agreement above 98% across all time points, substantially reducing turnaround times by 16–20 hours for ID and 32–48 hours for susceptibility results, thereby enabling earlier targeted therapy and improved management of bloodstream infections.
  

Regina J, Ianculescu N, Tzimas G, Monney P, Niclauss L, Kirsch M, et al. Rethinking the routine: are repeat blood cultures necessary after completion of infective endocarditis treatment? Clin Infect Dis. 2025 Nov 12; doi:10.1093/cid/ciaf617

• Summary: In a study of 598 infective endocarditis episodes, follow-up blood cultures performed within 14 days of completing antimicrobial therapy detected only 1.5% of recurrences and missed 6% of additional recurrences occurring between days 15 and 120, highlighting the limited utility of early post-treatment blood culture monitoring for detecting relapse.
  
• Editorial Commentary:
  DeSimone DC, Baddour LM. Post treatment blood cultures in patients with infective endocarditis: valuable, inconsequential or worse? Clin Infect Dis. 2025 Nov 12; doi:10.1093/cid/ciaf618

Improving Clinical Trials

Doleman B, Hardman JG. Core concepts in statistics and research methods. Part 5: systematic review and meta-analysis. BJA Educ. 2025 Nov 5; doi:10.1016/j.bjae.2025.10.002

• Summary: This article explains what systematic reviews and meta-analyses are and when to perform them, emphasizes that despite their traditional placement atop the evidence hierarchy high-certainty findings are uncommon due to biases and errors, and provides practical guidance—using the GRADE framework (risk of bias, publication bias, indirectness, imprecision, heterogeneity)—to appraise certainty and apply meta-analyses judiciously in clinical decision-making.

Mitchell EJ, Arundel C, Babalis D, Connolly S, Constable L, Goodman K, et al. Supporting the professional development of trial managers: how can you help? Trials. 2025 Oct 24;26:436. doi:10.1186/s13063-025-09199-6

• Summary: This article underscores the pivotal yet often undervalued role of clinical trial managers—who lack clear career pathways and face limited professional growth, particularly in UK academic-led trials within universities/NHS trusts and UKCRC-registered CTUs—and offers practical guidance for managers and employers to enhance professional development and better support this essential workforce.

Moreno R, Rhodes A, Ranzani O, Salluh JIF, Berger-Estilita J, Coopersmith CM, et al. Rationale and methodological approach underlying the development of the Sequential Organ Failure Assessment (SOFA)–2 score: a consensus statement. JAMA Netw Open. 2025 Oct 29;8(10):e2545040. doi:10.1001/jamanetworkopen.2025.45040

• Summary: Through a modified Delphi process, systematic reviews, and validation in datasets covering 3,339,470 ICU patients across 9 countries, a 60-expert task force developed SOFA-2—an updated Sequential Organ Failure Assessment with contemporary definitions, new variables encompassing physiological/laboratory measures and pharmacologic/mechanical organ support, and revised 0–4 severity thresholds—demonstrating content, construct, and predictive validity and better reflecting current critical care practice and organ dysfunction–associated outcomes.

Clack L, Schultes MT, Albers B, Wolfensberger A. Hybrid effectiveness-implementation studies in infection prevention and infectious diseases: a narrative review. Clin Microbiol Infect. 2025 Oct 30; doi:10.1016/j.cmi.2025.10.022

• Summary: This narrative review surveys hybrid effectiveness–implementation studies in infection prevention and control and infectious diseases—cataloguing existing studies and protocols, the interventions and implementation strategies used, and the effectiveness and implementation outcomes reported—to highlight how hybrid designs can accelerate translation despite limited current use, and to identify gaps and opportunities to advance IPC/ID research and practice.

Hovsepjan V, Thijs A, van Diemen JJK, Bogaards JA, Winter MM, Bosmans JE, et al. Aspirin to prevent cardiovascular events in patients with community-acquired pneumonia or influenza (ASCAP study): protocol for a multicentre, randomised, double-blind, placebo-controlled trial. BMJ Open. 2025;15:e110210. doi:10.1136/bmjopen-2025-110210

• Summary: The ASCAP study is a multicentre, double-blind, placebo-controlled randomized trial in the Netherlands evaluating whether adding aspirin to standard therapy in adults hospitalized with moderate-to-severe community-acquired pneumonia or influenza can reduce the incidence of acute coronary syndrome (ACS) and other major cardiovascular events over 180 days, while also monitoring bleeding risk, mortality, quality of life, and societal costs; the trial aims to enroll 760 patients to detect a 60% hazard reduction in ACS, with 114 patients currently enrolled.
  

van Werkhoven CH. Too close to the sun? Why our cluster-randomized trial was terminated. CMI Comms. 2025 Oct 30; doi:10.1016/j.cmicom.2025.105145

• Summary: The SAGA trial, designed to evaluate short-course aminoglycosides as adjunctive therapy in adults with community-onset sepsis, was prematurely terminated due to slow patient recruitment and low compliance with the allocated antibiotic regimens, which would have reduced the trial’s power from 80% to 40% and required an impractical 10-year extension; this decision, while difficult, highlights the importance of early risk assessment, ongoing monitoring of enrolment and adherence, and readiness to make informed decisions when trial feasibility is compromised.
  

Stupica D, Kejžar N. Which trial do we need? Corticosteroid therapy in Lyme borreliosis–associated facial palsy: a double-blind placebo-controlled multicentre randomized trial. Clin Microbiol Infect. 2025 Nov 12; doi:10.1016/j.cmi.2025.11.007

• Summary: Lyme borreliosis (LB) is the most common tick-borne infection in the Northern Hemisphere, with Lyme neuroborreliosis being its most frequent extracutaneous manifestation and facial palsy the predominant clinical feature; differentiating LB-associated from idiopathic facial palsy is crucial as the former requires antibiotics, whereas corticosteroids are recommended for the latter, yet there is currently no clear guideline on adjunctive corticosteroid use in LB-associated facial palsy due to limited, small, and inconsistent studies, highlighting the need for multicentre, high-quality trials with standardized clinical assessment to determine whether corticosteroids improve outcomes.

General Interest

Hamon A, Grégory J, Kimseng H, Lamamri M. Septic shock secondary to a rat-bite fever. Intensive Care Med. 2025 Oct 21; doi:10.1007/s00134-025-08148-w

• Summary: This case reports a rare Streptobacillus moniliformis infection causing spondylodiscitis with possible endocarditis and septic shock, identified only through anaerobic blood culture and 16S rRNA PCR, highlighting diagnostic challenges with fastidious pathogens and the need to consider zoonotic exposure in severe infections.

Van den Eynde J, van der Pluijm C, Schellekens P, Vanhoutte T, Bammens B. Spiraling into a distant past. N Engl J Med. 2025 Nov 5;393(18):1844–1850. doi:10.1056/NEJMcps2507868

• Summary: An 83-year-old man with recent unilateral facial-nerve palsy treated with methylprednisolone developed generalized pruritus, progressive edema (legs, face, arms/hands), arthralgias, malaise, anorexia, 5 kg weight gain, and dark urine over a month, with persistently abnormal liver tests showing markedly elevated alkaline phosphatase, raised ALT/AST, hypoalbuminemia, and high CRP; abdominal ultrasound revealed hepatic steatosis and splenomegaly without biliary dilation or stones, and extensive viral serologies were negative.

Alsabri M, Onyejesi CD, Patel A, Elewa M, Abady EM, Mohunsing R, et al. Optimizing fever management in pediatric emergency medicine: pathophysiology, diagnostics, and evidence-based strategies. Int J Emerg Med. 2025 Nov 5;18:231. doi:10.1186/s12245-025-01014-y

• Summary: This comprehensive pediatric review examines fever’s dual role as a protective immune response and potential risk, highlights diagnostic challenges and evidence-based management—especially for neonates and immunocompromised children—addresses parental perceptions and antipyretic overuse, notes global treatment disparities and the emerging contributions of AI and digital health, and calls for refined biomarkers and strengthened antimicrobial stewardship to improve clinical decision-making and outcomes while curbing antibiotic resistance.

Campodonico J, Lauri C, Pezzuto B, Agostoni P, Vignati C. Evolution in the diagnosis and treatment of myocarditis in recent years: state of the art. J Clin Med. 2025 Oct 28;14(21):7661. doi:10.3390/jcm14217661

• Summary: Acute myocarditis spans infections, toxins, and immune-mediated causes (with viruses predominant), now increasingly includes immune checkpoint inhibitor–associated cases and genetic predisposition (e.g., arrhythmogenic cardiomyopathy variants), and benefits from diagnostic advances—high-sensitivity troponins and cardiac MRI per updated 2018 Lake Louise Criteria (T1/T2 mapping) for inflammation/fibrosis, plus endomyocardial biopsy (especially early within 48 hours in fulminant disease) with immunohistochemistry to subtype disease—while treatment is etiology-specific (immunosuppression for eosinophilic and giant cell myocarditis or autoimmune forms) and otherwise centers on evidence-based acute heart failure care and supportive therapy.

Poole AP, Chaba A, Bellomo R, Bailey M, Deane A, Delaney A, et al. Mortality trends for sepsis and septic shock among critically ill adults in Australia and New Zealand. Intensive Care Med. 2025 Nov 3; doi:10.1007/s00134-025-08162-y

• Summary: In a 23-year analysis of 303,389 adult sepsis admissions across 219 ICUs in Australia and New Zealand, in-hospital mortality fell from 28% in 2000 to a nadir of 11% in 2020 (overall adjusted OR 0.48, 95% CI 0.43–0.54), with annual declines of 1.1% (2000–2013) and 0.3% (2013–2020) followed by a 0.9% rise per year (2020–2023) to 13% in 2023, and remained substantially higher in septic shock (25%) and among patients receiving invasive mechanical ventilation (20%).

Estrella MM, Ballew SH, Sang Y, Grams ME, Coresh J, Surapaneni A, et al. Discordance in creatinine- and cystatin C–based eGFR and clinical outcomes: a meta-analysis. JAMA. 2025 Nov 7; doi:10.1001/jama.2025.17578

• Summary: In an individual-level meta-analysis from the CKD Prognosis Consortium (23 outpatient and 2 inpatient cohorts; n≈861,000), 11% of outpatients and 35% of inpatients had cystatin C–based eGFR at least 30% lower than creatinine-based eGFR, and this discordance was associated with substantially higher risks of all-cause and cardiovascular mortality, atherosclerotic cardiovascular disease, heart failure, and kidney failure requiring replacement therapy over ~11 years, indicating prognostic significance when eGFRcys is markedly lower than eGFRcr.
• Editorial:
  Sarav M, Alpern RJ. Divergent GFR estimates and clinical implications. JAMA. 2025 Nov 7; doi:10.1001/jama.2025.14043

Liu KD, Siew ED, Tuot DS, Vijayan A, Umemoto GM, Birkelo BC, et al. A conservative dialysis strategy and kidney function recovery in dialysis-requiring acute kidney injury: the Liberation From Acute Dialysis (LIBERATE-D) randomized clinical trial. JAMA. 2025 Nov 7; doi:10.1001/jama.2025.21530

• Summary: In a multicenter randomized trial of 220 adults with dialysis-requiring acute kidney injury, a conservative dialysis strategy (initiating dialysis only for specific metabolic/clinical indications) increased unadjusted recovery of kidney function at discharge versus thrice-weekly conventional dialysis (64% vs 50%; absolute difference 13.8%, P=.04), reduced dialysis frequency and dialysis-associated hypotension, and yielded more dialysis-free days by day 28, suggesting this approach may hasten recovery but warrants confirmation in larger studies.
• Editorial:
  Waikar SS. A-E-I-O-U and sometimes why—dialysis in acute kidney injury. JAMA. 2025 Nov 7; doi:10.1001/jama.2025.21618

Gomes MS, Britto-Costa LF, Levin AS, Ho YL. Perception of the hospitalization process among survivors of carbapenem-resistant Acinetobacter baumannii bacteremia: a qualitative study. Am J Infect Control. 2025 Oct 28; doi:10.1016/j.ajic.2025.10.019

• Summary: In qualitative interviews with nine survivors of carbapenem-resistant Acinetobacter baumannii bacteremia, participants described profound post-hospital emotional and physical impacts, systemic communication gaps (limited explanations about procedures/devices and the infection, poor understanding of antibiotic resistance, some unaware of their CRAB diagnosis), and hesitancy to speak up, leading the authors to recommend structured HAI education and patient-engaged safety (e.g., scripted bedside hand-hygiene reminders with teach-back, plain-language leaflets, and co-designed bedside posters) to improve understanding, autonomy, and shared prevention.

Dellière S, Seidel D, Ferré VM, Agrawal R, Baron A, Berti V, et al. Gender differences in audience participation at infectious disease and microbiology conferences: a prospective observational study. Clin Microbiol Infect. 2025 Nov 12; doi:10.1016/j.cmi.2025.11.005

• Summary: Women are underrepresented in audience participation at infectious disease and clinical microbiology conferences despite delivering nearly half of all presentations, accounting for only 36.4% of interventions. Factors that increase women’s participation include having female moderators and women asking the first question. Addressing these participation gaps is essential to promote equity, enhance visibility, empower women in STEM, and strengthen scientific innovation.

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