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Issue: Newsletter 10 | December 1, 2025

Randomised Controlled Trials

Citation of Articles PICO Main Results Risk of Bias
File TM Jr, Kaye KS, Skliarov I, Hovbakh I, Katsarava V, Kirsch C, et al. Omadacycline versus moxifloxacin for community-acquired bacterial pneumonia (OPTIC-2): a phase 3b, randomised, double-blind, multicentre, controlled, noninferiority trial. EClinicalMedicine. 2025 Dec 20;90:103656. doi:10.1016/j.eclinm.2025.103656 P: 670 adults with community-acquired bacterial pneumonia (PSI class III–IV; ~50% >65 years)
I: Omadacycline (100 mg IV q12h for two doses, then 100 mg IV daily; optional switch to 300 mg oral daily after ≥2 days; total 7–10 days)
C: Moxifloxacin (400 mg IV daily; optional 400 mg oral daily after ≥2 days; total 7–10 days)
O: Early clinical response at 72–120 h; clinical response at post-therapy evaluation (5–10 days after last dose); microbiologic response by subject and pathogen; safety and treatment-emergent adverse events (TEAEs)		 Omadacycline was noninferior to moxifloxacin for early clinical response (89.6% vs 87.7%, difference 1.9%, 95% CI –3.0 to 6.8) and for post-therapy clinical response (86.0% vs 87.7%, difference –1.7%, 95% CI –6.9 to 3.4). Clinical success across key pathogens was high and comparable between groups (omadacycline 74.4–100% vs moxifloxacin 75.0–97.4%). Safety was acceptable, with similar rates of common TEAEs; headache (3.6% vs 4.5%) and mild lab abnormalities were the most frequent, with diarrhoea more common in the moxifloxacin group. Overall, omadacycline was effective, well tolerated, and provided a viable once-daily IV-to-oral monotherapy option for CABP. Low-to-moderate risk: The randomised, double-blind design reduces performance and detection bias, although industry sponsorship may introduce potential bias in conduct or reporting. Large sample size and balanced groups support internal validity. High follow-up completion and objective clinical endpoints limit attrition and assessment bias. Generalisability may be somewhat limited by the Eastern European study population and predominance of PSI class III patients.
Medel-Jara PA, Latorre G, Fuentes-Lopez E, Pizarro M, Viviani P, Chahuan J, et al. Comparison between optimized bismuth quadruple therapy and standard clarithromycin-based triple therapy for first-line Helicobacter pylori eradication: a double-blind randomized controlled trial. Lancet Reg Health Am. 2026 Jan;53:101312. doi:10.1016/j.lana.2025.101312 P: 127 treatment-naïve adults in Chile with confirmed active H. pylori infection
I: Optimized bismuth quadruple therapy for 14 days (esomeprazole 40 mg TID, amoxicillin 1 g TID, metronidazole 500 mg TID, bismuth subsalicylate 369 mg TID)
C: Standard triple therapy for 14 days (omeprazole 20 mg BID, amoxicillin 1 g BID, clarithromycin 500 mg BID)
O: Successful H. pylori eradication ≥4 weeks post-treatment; adverse events; clarithromycin resistance; CYP2C19 genotype effects		 Optimized bismuth quadruple therapy achieved significantly higher eradication rates than standard triple therapy in intention-to-treat analysis (95% vs 81%, p=0.033). Adverse event rates were similar between groups (67% vs 66%), with no differences in baseline clarithromycin resistance or CYP2C19 polymorphisms. Overall, the optimized bismuth quadruple regimen provided superior eradication efficacy without added toxicity or reduced adherence. Moderate risk: The randomized double-blind design minimizes performance and detection bias, and balanced baseline characteristics strengthen comparability. The relatively small sample size limits precision, and single-country recruitment may constrain generalizability. Adherence and outcome assessment appear robust, but microbiologic confirmation timing may introduce minor misclassification risk.
Abaft S, Yasin Z, Ahmadinia M, Eshraghi A, Gholizadeh Niari B, Minaeian S, et al. Efficacy and safety of colistin–doxycycline combination therapy in multi-drug resistance Gram-negative infections: a double-blind randomized controlled trial. Infection. 2025 Nov 20; doi:10.1007/s15010-025-02698-3 P: 46 adults hospitalized with culture-confirmed multidrug-resistant Klebsiella pneumoniae infections
I: Colistin–doxycycline combination therapy
C: Colistin–meropenem combination therapy
O: Clinical cure (resolution without therapy escalation and in-hospital mortality); microbiological eradication; acute kidney injury; treatment-related adverse events; inflammatory resolution; need for mechanical ventilation		 Colistin–doxycycline achieved significantly higher clinical cure rates than colistin–meropenem (87.0% vs 46.7%, p=0.012) and lower mortality (69.6% vs 86.7%, p=0.017). Microbiological eradication was also superior (p=0.016). Nephrotoxicity was numerically lower in the colistin–doxycycline arm (19.1% vs 33.3%, p=0.092), with faster resolution of inflammatory markers and reduced need for mechanical ventilation (60.9% vs 33.3%, p=0.028). Overall, colistin–doxycycline demonstrated improved efficacy with a favorable safety profile compared with colistin–meropenem. High-to-moderate risk: Although double-blind randomization reduces performance and detection bias, the small sample size (n=46) limits power and increases imprecision. Single-center recruitment and heterogeneous infection severity constrain generalisability. Short follow-up and combined primary endpoint may introduce outcome misclassification. Despite balanced allocation, the small cohort increases susceptibility to chance imbalances and type I error.
Lissauer D, Gadama L, Waitt C, Whyte S, Burnside G, Anilkumar A, et al. A multicomponent intervention to improve maternal infection outcomes. N Engl J Med. 2025 Nov 19; doi:10.1056/NEJMoa2512698 P: 431,394 women who were pregnant or recently pregnant across 59 health facilities in Malawi and Uganda
I: APT-Sepsis multicomponent program (supporting adherence to WHO hand hygiene, evidence-based infection prevention and management practices, and early sepsis detection using the FAST-M bundle: fluids, antibiotics, source control, transfer, monitoring)
C: Usual care with standard guideline dissemination
O: Composite of infection-related maternal death, infection-related near-miss event, or severe infection-related illness (deep surgical-site, deep perineal, or body-cavity infection)		 The APT-Sepsis program significantly reduced the composite primary outcome compared with usual care (1.4% vs 1.9%; risk ratio 0.68, 95% CI 0.55–0.83, P<0.001). The effect was consistent across countries, across facilities of varying sizes, and was sustained over time. The intervention improved adherence to evidence-based infection prevention and management practices and enabled earlier identification and treatment of maternal sepsis through implementation of the FAST-M bundle. Moderate risk: The cluster-randomized design reduces contamination but may introduce imbalance between facilities. Blinding of facilities and providers was not feasible, introducing potential performance bias. However, the extremely large sample size, consistency of effects across clusters, and objective clinical outcome measures strengthen internal validity. Some risk of detection bias remains due to reliance on facility-reported outcomes.
de Mesmay M, Geral L, Gregoire C, Roy M, Welschbillig S, Le Cossec C, et al. Effect of paracetamol on cerebral temperature in febrile brain-injured patients: the NEUROTHERM study, a randomized controlled pharmacodynamic trial. Crit Care Med. 2025 Nov 11; doi:10.1097/CCM.0000000000006951 P: 99 febrile brain-injured ICU patients (mean age 55 ± 13 yr; 24% female) with cerebral temperature ≥38.5°C for >30 min and monitored via intracerebral thermal probe
I: Single IV administration of paracetamol
C: Placebo (single IV dose)
O: Mean cerebral temperature over 6 hours; systemic temperature; time with cerebral temperature <38.5°C; hemodynamic effects; proportion of non-responders		 Paracetamol significantly reduced mean cerebral temperature over 6 hours compared with placebo (38.4 ± 0.5°C vs 39.0 ± 0.5°C, p<0.001), with cerebral temperatures consistently higher than systemic temperatures in both groups. Patients receiving paracetamol spent markedly more time below 38.5°C (median 215 min vs 0 min, p<0.001). Approximately 30% were non-responders, but responders experienced a 1°C drop. Paracetamol caused modest reductions in systolic blood pressure and heart rate without other major adverse effects. Moderate risk: The randomized double-blind placebo-controlled design minimizes performance and detection bias. Small sample size limits precision and increases susceptibility to imbalances. Single-center Neuro-ICU setting limits generalizability. Short follow-up captures acute pharmacodynamic response but not longer-term outcomes. Cerebral temperature monitoring is objective, reducing measurement bias.
Robinson AL, Boyle MG, Hogan PG, Malone SM, Krauss MJ, Richardson LM, et al. Evaluating personal and environmental decolonization strategies for children with skin and soft tissue infection and their households: a randomized clinical trial. Clin Infect Dis. 2025 Nov 24;ciaf627. doi:10.1093/cid/ciaf627 P: 196 children with community-associated Staphylococcus aureus SSTI and 623 household contacts (entire household enrolled)
I: Periodic-Personal decolonization (twice-weekly chlorhexidine bathing + monthly intranasal mupirocin), Environmental-Hygiene (weekly surface disinfection + enhanced laundry), or an Integrated-Approach combining both (primary comparison: Integrated vs combined other two groups)
C: Combined comparator of Periodic-Personal or Environmental-Hygiene interventions
O: Household-level cumulative SSTI at 3 months; SSTI incidence at 6 and 9 months; personal and household S. aureus colonization (MRSA/MSSA)		 Cumulative SSTI incidence at 3 months did not differ between the Integrated-Approach and the combined Periodic-Personal and Environmental-Hygiene groups. However, among index patients and contacts with SSTI in the prior year, the Integrated-Approach resulted in lower SSTI incidence at 6 and 9 months. Multivariable analyses showed prior-year SSTI strongly predicted subsequent SSTI, whereas intervention group assignment was not a significant predictor. All interventions reduced MRSA—though not MSSA—personal colonization over 9 months, and environmental interventions did not significantly affect overall SSTI outcomes. Moderate risk: The open-label design introduces performance and detection bias, especially with behavior-dependent interventions. Clustered household enrollment reduces contamination but increases complexity and risk of imbalance. Long enrollment period (2015–2021) may introduce temporal confounding. Outcome assessment relied partly on self-reported SSTIs, adding potential misclassification. Nevertheless, randomization, structured follow-up, and biological sampling strengthen internal validity.
Sun F, Li Y, Zhang Y, Cai C, Chen Y, Yi H, et al. A 6 to 9-month oral regimen for rifampicin-resistant tuberculosis: a randomised open-label non-inferiority trial in China. Clin Microbiol Infect. 2025 Nov 23; doi:10.1016/j.cmi.2025.11.015 P: 354 adults in China with rifampicin-resistant pulmonary tuberculosis (randomized from 660 screened)
I: 6–9-month all-oral regimen: levofloxacin, linezolid, cycloserine, clofazimine and/or pyrazinamide
C: 9-month injectable-containing regimen (control)
O: Favourable outcome at 84 weeks (two consecutive negative cultures with no prior unfavourable outcome); grade 3–5 adverse events		 The all-oral regimen was noninferior to the injectable-containing regimen, with higher favourable outcomes in the modified intention-to-treat population (76.1% vs 63.7%, difference 12.4%, 95% CI 2.4–22.5) and in per-protocol analysis (84.4% vs 73.5%, difference 10.9%, 95% CI 1.1–20.7). Severe adverse events were less frequent in the oral regimen (59.5% vs 69.1%), particularly QTcF prolongation (29.5% vs 44.6%) and hepatobiliary disorders (7.5% vs 21.7%). Overall, the all-oral regimen demonstrated better tolerability and comparable or superior efficacy. Moderate risk: The open-label design may introduce performance and detection bias, though objective culture-based primary outcomes mitigate this. Randomization and predefined noninferiority margins strengthen internal validity. However, only 354 of 660 screened participants were randomized, raising potential selection bias. Differential follow-up across treatment durations and reliance on per-protocol analysis add risk of attrition bias. Generalizability is limited to similar programmatic TB settings without access to newer WHO-recommended drugs.

Target Trial Emulation

Reep CAT, Wils EJ, Heunks L. Opportunities, challenges and future perspectives for target trial emulation in critical care clinical research. Crit Care. 2025 Nov 12;29:484. doi:10.1186/s13054-025-05723-x

  • Summary: This review explains how target trial emulation (TTE) can strengthen causal inference in observational research—highlighting its core assumptions, common biases it helps avoid, practical challenges in dynamic clinical settings like ventilation decisions, and key considerations for designing high-quality emulations that clinicians and researchers can critically evaluate.

Antibiotics

Ahmadi F, McArthur E, Garcia-Bournissen F, Rieder MJ, Muanda FT. Trimethoprim-sulfamethoxazole and acute respiratory failure in adolescents and young adults. JAMA Netw Open. 2025 Nov 24;8(11):e2545251. doi:10.1001/jamanetworkopen.2025.45251

  • Summary: This large population-based cohort study of adolescents and young adults found that initiating trimethoprim-sulfamethoxazole (TMP-SMX) was associated with a small but significantly higher 30-day risk of hospital visits for acute respiratory failure compared with amoxicillin or cephalosporins, reinforcing FDA safety warnings and suggesting clinicians and regulators should carefully balance risks when prescribing TMP-SMX and consider updates to labeling and guidelines.

Rodríguez-Baño J. New drugs against multidrug-resistant Gram negatives: endangered species. Clin Microbiol Infect. 2025 Nov 25; doi:10.1016/j.cmi.2025.11.022

  • Summary: This overview highlights how the emergence of difficult-to-treat Gram-negative infections, coupled with warnings from clinicians and major public health agencies (ECDC, CDC, WHO), spurred urgent global initiatives to accelerate research and development of new antibacterial therapies after a period of severely limited treatment options.

Hu S, Jiang L, Xu H, Meng X, Zhang D, Zhou D, et al. Eravacycline and omadacycline rescue multidrug-resistant Elizabethkingia anophelis: triple-model evaluation across in vitro, Galleria mellonella, and murine bacteremia systems. J Adv Res. 2025 Nov 24; doi:10.1016/j.jare.2025.11.048

  • Summary: This study provides the first comprehensive in vitro and in vivo evidence that the fluorocyclines eravacycline and omadacycline exhibit potent activity against multidrug-resistant Elizabethkingia anophelis, showing extremely low MICs, improved survival in Galleria larvae, marked bacterial load reduction and anti-inflammatory effects in murine models, and even complete tissue eradication with eravacycline—supporting their potential role in optimizing clinical management and warranting future clinical trials.

Bhavnani SM, Hammel JP, Onufrak NJ, Pogue JM, Jones RN, Sader HS, et al. Evaluation of aminoglycoside dosing regimens adjusted for renal function and in vitro susceptibility test interpretive criteria for Enterobacterales and Pseudomonas aeruginosa: brief summary. Open Forum Infect Dis. 2025 Dec;12(12):ofaf427. doi:10.1093/ofid/ofaf427

  • Summary: This pharmacometric analysis supports updated, renal function–adjusted dosing regimens for aminoglycosides and recommends revised susceptibility and therapeutic drug monitoring–based breakpoints for amikacin, gentamicin, and tobramycin against Enterobacterales and Pseudomonas aeruginosa, enabling more adaptable and clinically appropriate treatment strategies.

Falagas ME, Kontogiannis DS, Romanos LT, Ragias D, Agoranou ME, Kakoullis SA, et al. Intravenous fosfomycin for gram-negative and gram-positive bacterial infections: a systematic review of the clinical evidence. Antibiotics. 2025 Nov 23;14(12):1193. doi:10.3390/antibiotics14121193

  • Summary: This systematic review of 53 studies shows that intravenous fosfomycin—used alone or in combination—provides safety and efficacy comparable to or better than other antibiotics for a wide range of Gram-negative and Gram-positive infections (including Enterobacterales, P. aeruginosa, A. baumannii, Staphylococcus, and Enterococcus), with manageable electrolyte-related adverse effects, supporting its role especially in critically ill patients and deep-seated infections despite study heterogeneity.

Raber SR, Xie R, Rogers H, Soto E, Arhin FF, Stone GG, et al. Microbiological, clinical, and pharmacokinetic/pharmacodynamic data to support EUCAST aztreonam–avibactam minimum inhibitory concentration susceptibility breakpoints against Enterobacterales. Infect Dis Ther. 2025 Nov 21; doi:10.1007/s40121-025-01267-3

  • Summary: This analysis integrates pharmacokinetic/pharmacodynamic modeling, global MIC surveillance of over 100,000 Enterobacterales isolates, and clinical trial data to support an aztreonam–avibactam susceptible breakpoint of ≤8 mg/L, showing high predicted target attainment and no decline in clinical response at higher MICs; however, sparse clinical data for isolates with MIC ≥4 mg/L justify the more conservative EUCAST breakpoint of ≤4 mg/L.

Prytz KL, 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: This prospective ICU study found that patients with community-acquired sepsis frequently experienced either subtherapeutic or excessively high β-lactam antibiotic levels during the first 48 hours, with younger, less comorbid patients more likely to have low concentrations and those with higher creatinine and noradrenaline requirements more likely to have very high levels, underscoring the need for therapeutic drug monitoring and model-informed precision dosing to optimize early antibiotic therapy and reduce risks of treatment failure or toxicity.

Bekker A, Panjasawatwong N, Hill LF, Stohr W, Walker AS, Ellis S, et al. Pharmacokinetics and safety of fosfomycin and flomoxef administered as part of neonatal sepsis treatment (NeoSep1 part 1). Antimicrob Agents Chemother. 2025; doi:10.1128/aac

  • Summary: In this pharmacokinetic and safety study of 62 mostly preterm neonates with suspected sepsis, fosfomycin and flomoxef showed predictable age-dependent clearance, achieved high probability of target attainment at clinically relevant MICs, and were generally well tolerated with only mild to moderate antibiotic-related adverse events, supporting the proposed neonatal dosing regimens for the upcoming NeoSep1 randomized trial.

Kent JE, Elane M, Leyn S, Zlamal J, Wong N, Aizin M, et al. Mutations in two-component signaling systems drive experimental evolution of tigecycline and colistin resistance in Acinetobacter baumannii. Antimicrob Agents Chemother. 2025 Oct 29; doi:10.1128/aac.00809-25

  • Summary: Using a morbidostat to track real-time evolution under tigecycline and colistin pressure, this study mapped the key resistance-driving mutations in Acinetobacter baumannii—primarily adeSR and trm alterations for tigecycline resistance and pmrCAB mutations for colistin resistance—revealing distinct evolutionary pathways, low global prevalence of these mutations in public genomes, and providing a foundational framework for predictive “resistomics” beyond traditional resistance-gene profiling.

Bonazzetti C, Grechi A, Gibertoni D, Mangione L, Todisco F, Tonnini M, et al. Implementation of a bundle for the management of patients with gram-negative bloodstream infection: a pre-post quasi-experimental study. Open Forum Infect Dis. 2025 Nov;12(11):ofaf680. doi:10.1093/ofid/ofaf680

  • Summary: In this quasi-experimental study of 2683 adults with gram-negative bloodstream infection, implementing a standardized management bundle—including structured follow-up blood cultures, imaging rules, optimized β-lactam administration, and defined treatment durations—did not reduce 30-day mortality but significantly decreased new multidrug-resistant organism emergence, supporting its role in limiting antimicrobial resistance despite unchanged clinical survival outcomes.

Jan H-E, Wang J-L, Lee N-Y, Hsueh S-C, Huang Y-T, Ko W-C, Hsueh P-R. Ceftazidime-avibactam resistance among clinical isolates of Citrobacter freundii, Morganella morganii, Providencia spp. and Serratia marcescens across five continents: data from the ATLAS programme, 2016–2023. Int J Antimicrob Agents. 2025;107669. doi:10.1016/j.ijantimicag.2025.107669

  • Summary: This global analysis of nearly 19,000 isolates (2016–2023) shows rising ceftazidime–avibactam resistance—highest in Providencia spp. and increasing over time in Citrobacter freundii and Serratia marcescens—with substantial regional variation, strong associations with carbapenem resistance, and predominance of blaNDM (except blaKPC in S. marcescens), underscoring the need for ongoing worldwide surveillance.

Mendelson M, Afari-Asiedu S, Schellack N, Wertheim H, Mpundu M, Gautham M. Facing up to reality: over-the-counter access to antibiotics in low-income and middle-income countries needs a paradigm shift in thinking. Lancet Glob Health. 2025;13(12):e2175–e2179. doi:10.1016/S2214-109X(25)00394-8

  • Summary: This article argues that in the face of severe global shortages of health-care professionals, widespread lack of access to essential health services, and millions of preventable deaths from treatable infections—especially in low- and middle-income countries—over-the-counter antibiotic sellers should be reframed from being seen solely as contributors to misuse to being recognised as essential, politically and economically embedded access points, and integrated into antibiotic stewardship through targeted training, point-of-care diagnostics, limited quality-assured antibiotic formularies, and robust monitoring systems, ultimately positioning them as part of a pragmatic solution to expand safe and equitable antibiotic access.

Dorazio AJ, Aitken SL, Pierce VM, Kline EG, Squires KM, Pogue JM, Shields RK. First report of treatment-emergent resistance to cefepime-zidebactam in Pseudomonas aeruginosa. Clin Infect Dis. 2025; ciaf638. doi:10.1093/cid/ciaf638

  • Summary: This article reports the first documented case of treatment-emergent resistance to cefepime-zidebactam in a patient with Pseudomonas aeruginosa pneumonia, where the MIC rose substantially during therapy and whole-genome sequencing revealed new MexAB-OprM efflux pump mutations that led to clinical failure and cross-resistance to ceftazidime-avibactam and imipenem-relebactam.

Grégoire N, Mbarga D, Mirfendereski H, Stanke-Labesque F, Breilh D, Forestier E, Ferry T, Goutelle S, Gavazzi G, Brunet T, Paccalin M, Roubaud-Baudron C; the Infectiology and Geriatrics InterGroup (SPILF-SFGG GInGer). Evaluation of subcutaneous amoxicillin/clavulanic acid pharmacokinetics as an alternative to the intravenous route in older patients—the PhASAge Study. J Antimicrob Chemother. 2025; dkaf381. doi:10.1093/jac/dkaf381

  • Summary: This study evaluated the pharmacokinetics and safety of subcutaneous amoxicillin/clavulanic acid in older adults and found that SC administration achieved 78–82% bioavailability compared with IV dosing, maintained therapeutically relevant amoxicillin concentrations despite lower Cmax, and was well tolerated, supporting its use as a practical alternative when oral or IV routes are limited.

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

  • Summary: This review outlines the limitations of MIC as a single-timepoint pharmacodynamic metric and summarizes a range of published antibiotic PD measures—categorized by data requirements—to help clinicians and researchers choose more informative tools, emphasizing how pharmacometric modeling can better capture bacterial dynamics and guide rational, optimized antibiotic therapy.

Mansouri A, Durazzi F, Ihsan MA, Griffin S, Manfreda G, Valdramidis VP, Pasquali F, Remondini D. Identification of antimicrobial resistance genes in Escherichia coli through network diffusion. J Antimicrob Chemother. 2025; dkaf404. doi:10.1093/jac/dkaf404

  • Summary: This study used network diffusion analysis on E. coli protein interactomes to identify AMR-related genes and pathways, validated several candidates through knockout susceptibility testing, and demonstrated that systems-biology–guided network modeling can reveal previously unrecognized contributors to resistance and highlight potential new drug targets.

Mitaka H, Hasegawa S, Lan KF, Jain R, Rakita RM, Pottinger PS. Characterizing Ertapenem Neurotoxicity: A Systematic Review and Experience at a Tertiary Medical Center. Open Forum Infectious Diseases. 2024;11(5):ofae214. doi:10.1093/ofid/ofae214

  • Summary: This systematic review and case series of 125 patients highlights that ertapenem-associated neurotoxicity—most often presenting as seizures, delirium, or hallucinations—occurs primarily in older adults with renal dysfunction or underlying CNS conditions, typically within four days of therapy, indicating a higher-than-recognized incidence and underscoring the need for prospective studies to better define risk and outcomes.

Rodríguez-Ochoa JL, Saúco-Carballo C, Pérez-Palacios P, Merino-Bohórquez V, Velázquez-Escudero A, López-Cerero L, et al. Pharmacokinetic/pharmacodynamic optimization of temocillin treatment against CTX-M-15-producing Klebsiella pneumoniae isolates in a hollow-fiber infection model. Antimicrob Agents Chemother. 2025. doi:10.1128/aac.00946-25

  • Summary: Using a hollow-fiber infection model against CTX-M-15–producing Klebsiella pneumoniae, this study found that while both intermittent and continuous temocillin infusion rapidly reduced bacterial burden, continuous infusion provided more sustained suppression and better prevented resistance—often linked to cpxA mutations—supporting its potential clinical advantage and the need for further validation.

Zhang H, Liang B, Tan Z, Wang R, Cai Y. The synergistic activity of tigecycline-based combinations against multidrug-resistant Acinetobacter baumannii caused bloodstream infections. J Antimicrob Chemother. 2025. doi:10.1093/jac/dkaf386

  • Summary: This study identified meropenem as the strongest synergistic partner for tigecycline against multidrug-resistant Acinetobacter baumannii, showing that high-dose tigecycline plus meropenem achieved potent synergy in both in vitro PK/PD models and a lethal murine bloodstream infection model—but only for tigecycline-susceptible strains—supporting this combination as a promising treatment option for susceptible MDRAB BSIs.

Arun B, Liu E, Vallé Q, Sharma R, Bui NM, Mezcord V, Luu I, Traglia GM, Pasteran F, Paterson D, Bonomo RA, Ramirez MS, Rao GG. Ampicillin/Sulbactam in Combination with Ceftazidime/Avibactam Against Metallo-β-Lactamase-Producing Carbapenem-Resistant Acinetobacter baumannii: A Genomics-Informed Mechanism-Based Model. J Infect Dis. 2025. doi:10.1093/infdis/jiaf567

  • Summary: This study shows that combining ampicillin/sulbactam with ceftazidime/avibactam can significantly reduce bacterial burden in highly resistant carbapenem-resistant Acinetobacter baumannii strains, with mechanism-based modeling revealing how genomic resistance determinants shape drug potency and informing dose strategies—highlighting these β-lactam combinations as promising therapeutic options for difficult-to-treat CRAB infections.

Rinaldi M, Gatti M, Giannella M. Avoiding resistance development to newer drugs: open research lines. Clin Microbiol Infect. 2025. doi:10.1016/j.cmi.2025.11.009

  • Summary: This narrative review highlights strategies to prevent or slow resistance to newer β-lactam/β-lactamase inhibitor therapies for multidrug-resistant Gram-negative infections, emphasizing optimized PK/PD dosing (including continuous infusions and therapeutic drug monitoring), the uncertain but still investigational role of combination therapy, and promising non-antibiotic approaches—such as fecal microbiota transplantation, phage therapy, and immunization—that may reduce pathogen burden and help preserve the effectiveness of novel agents in high-risk populations.

Retamar-Gentil P, Beltrami M, Carrara E. New Drugs, Old Problems: A Narrative Review of Antibiotic Stewardship Program in the era of novel Gram-negative antibiotics. Clin Microbiol Infect. 2025. doi:10.1016/j.cmi.2025.11.011

  • Summary: This narrative review examines how antimicrobial stewardship programs can optimize the use of newly approved antibiotics for multidrug-resistant Gram-negative infections, highlighting that current evidence—though limited and mostly single-centre—supports strategies such as education, decision-support tools, PK/PD-guided dosing, and selective formulary restriction to improve appropriateness and outcomes, while underscoring the need for stronger real-world data, digital infrastructure, and standardized metrics to ensure sustainable and equitable implementation.

Miner TW, Callaway Kim K, Rothenberger S, Chaudhry S, Tadrous M, Suda KJ. Impact of implementation of World Health Organization National Action Plans on antibiotic rates: a time series analysis of 37 countries. Infect Control Hosp Epidemiol. 2025;46(11):1171–1174. doi:10.1017/ice.2025.10293

  • Summary: An interrupted time series analysis of 37 countries found that implementing National Action Plans on antimicrobial resistance had no consistent effect on antibiotic sales two years later, with individual countries showing highly variable outcomes ranging from substantial decreases to marked increases.

Hall RG II, Hooper L, Dissanaike S, Griswold JA, Kallem RR, Subramaniyan I, et al. Pharmacokinetics of ceftolozane/tazobactam in patients with partial- and full-thickness skin burns. Pharmacotherapy. 2025. doi:10.1002/phar.70076

  • Summary: In a small pharmacokinetic study of burn patients, ceftolozane/tazobactam exposure was broadly similar to healthy volunteers despite markedly higher interpatient variability, suggesting no routine dose adjustment is needed, though therapeutic drug monitoring or continuous infusion may be warranted when clinical response is suboptimal.

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. doi:10.1128/aem.01380-25

  • Summary: This study identifies and characterizes phiK2044, a highly potent lytic phage with broad activity against hypervirulent Klebsiella pneumoniae—including ST23 and K1 strains—demonstrating strong in vitro killing, effective bacterial clearance in mice, and a capsule-dependent infection mechanism via wcaJ, highlighting its therapeutic promise and value as a model for phage–host interaction research.

Bacterial Infections

Nguyen T, Bürkin F, Ayala-Montaño S, Acevedo Monterrosa I, Jonas D, Klotz D, et al. Prospective whole-genome sequencing to identify bacterial transmission and its modifiers in neonates. JAMA Netw Open. 2025 Nov 21;8(11):e2541409. doi:10.1001/jamanetworkopen.2025.41409

  • Summary: In this NICU cohort study of 434 infants, prospective whole-genome sequencing revealed that over half were colonized with multidrug-resistant or high-epidemic-potential bacteria and one-third of these colonizations resulted from transmission, identifying 37 clusters and showing that increased nurse staffing and prior antibiotic exposure reduced transmission risk while vascular catheter use increased it, demonstrating the value of sequencing for uncovering modifiable drivers of bacterial spread in neonatal care.

Paucard L, Varga B, Kermorvant-Duchemin E, Huynh B-T, Watier L. Hospital admissions after early-onset neonatal bacterial infection management guidelines in France. JAMA Netw Open. 2025 Nov 26;8(11):e2545436. doi:10.1001/jamanetworkopen.2025.45436

  • Summary: This nationwide French cohort study evaluated the impact of the 2017 guidelines that replaced routine microbiological sampling with clinical monitoring for asymptomatic newborns at risk of early-onset neonatal infection (EONI). Among 68,107 EONI hospitalizations from 2014–2023, rates of nonsevere EONI hospitalizations and EONI cases without NICU admission significantly decreased after the guideline change. Meanwhile, rates of severe EONI, NICU admissions, and late-onset neonatal bacterial infections remained unchanged. Overall hospitalization costs for EONI were reduced by half over the study period. These findings suggest that clinical monitoring safely reduced unnecessary hospitalizations without increasing severe or delayed infections.

Tanner WD, Mathew T, Roberts SC, Dieter L, Healy HG, Peaper DR, et al. Decontamination approaches and strategies for the prevention of sink drain-related healthcare-associated infections. Clin Microbiol Rev. 2025 Nov 21; doi:10.1128/cmr.00061-24

  • Summary: This narrative review examines how hospital sink drains act as persistent reservoirs for multidrug-resistant pathogens due to resilient wastewater biofilms, outlines why traditional cleaning methods often fail, describes documented decontamination and mitigation strategies from clinical and engineering literature, and highlights the urgent need for evidence-based, multidisciplinary guidance to prevent sink-associated healthcare outbreaks.

Britto C, Cavalli L, Senghore M, McAdam AJ, Hanage WP, Lu Y-J, et al. A 15-year single-center analysis of late-onset Group B Streptococcus infection correlating clinical severity with pathogen virulence determinants. Clin Infect Dis. 2025 Nov 25; doi:10.1093/cid/ciaf603

  • Summary: This study analyzed 87 invasive Group B Streptococcus isolates over 15 years using whole-genome sequencing and found that although severe infant disease frequently required ICU care or involved meningitis, no specific bacterial genomic traits predicted severity; late-onset and very late-onset disease were clinically and genomically similar, vaccine targets were broadly present, and resistance was mainly limited to macrolides, underscoring that host factors likely drive outcomes and suggesting current age-based disease classifications may need reevaluation.

Swets MC, Bakk Z, Westgeest AC, Ruffin F, Korn R, Jabbour J-F, et al. Reproducible identification of Staphylococcus aureus bacteremia clinical subphenotypes. Clin Infect Dis. 2025 Nov 27; doi:10.1093/cid/ciaf655

  • Summary: Across three large international cohorts—including one with high MRSA and USA300 prevalence—researchers consistently identified five reproducible clinical subphenotypes of Staphylococcus aureus bacteremia based on routine clinical data, showing that patient characteristics and acquisition patterns, rather than bacterial genotype, drive disease heterogeneity, with distinct groups exhibiting differing risks of mortality and persistent bacteremia, thus offering a practical framework to better understand and manage SAB complexity.

Song JS, Jung YK, Kweon S, Kang S-H, Kim MJ, Yoo J-J, et al. Next-generation sequencing improves detection of anaerobic and polymicrobial infections in pyogenic liver abscess. Clin Microbiol Infect. 2025 Nov 26; doi:10.1016/j.cmi.2025.11.018

  • Summary: This article highlights that although Klebsiella pneumoniae is widely regarded as the primary cause of pyogenic liver abscess in Asia, conventional culture methods may significantly underestimate the true microbial diversity—particularly polymicrobial and anaerobic contributors—raising concerns that current empiric treatment strategies may overlook important pathogens and require reassessment.

Min P, Yao J, Ruan S, Zhou L, Hua X, Li X, et al. Global phylogeography and genomic characterization of blaNDM-1-positive carbapenem-resistant Acinetobacter soli. J Antimicrob Chemother. 2025 Nov 24; doi:10.1093/jac/dkaf437

  • Summary: This study describes a blaNDM-1–positive Acinetobacter soli isolate and, through global genomic analysis, reveals that A. soli is widely distributed—especially in coastal regions of Asia—harbors clinically important resistance genes on stable plasmids, and may serve as an environmental reservoir for emerging antimicrobial resistance, underscoring the need for ongoing surveillance and One Health–based monitoring.

Beh JQ, Wick RR, Howden BP, Connor CH, Webb JR. Challenges and considerations for whole-genome-based antimicrobial resistance plasmid investigations. Antimicrob Agents Chemother. 2025 Nov 11; doi:10.1128/aac.01097-25

  • Summary: This review outlines how plasmids act as major vehicles for antimicrobial resistance, describes the vast genetic diversity and cross-species mobility of AMR plasmids, and highlights both the power and the limitations of whole-genome sequencing and current bioinformatic tools for studying them, emphasizing the need for improved databases and analytical methods to better leverage plasmid genomics for public health.

Koh V, Cabrera R, Sridatta PSR, Thevasagayam NM, Lim ZQ, Marimuthu K, et al. Plasmid dynamics driving carbapenemase gene dissemination in healthcare environments: a nationwide analysis of closed Enterobacterales genomes. Nat Commun. 2025;16:9522. doi:10.1038/s41467-025-64515-7

  • Summary: This nationwide genomic study of carbapenem-producing Enterobacterales in Singapore identified over a thousand closed carbapenemase-carrying plasmids and showed that two dominant plasmid genotypes (PC1 with blaKPC-2 and PC2 with blaNDM-1) drive most horizontal and vertical transmission events, with their conserved, low-cost genomes enabling stable propagation across species and patients, while less common plasmids carry additional metabolic genes that may influence their ecological niche.

Bai AD, Loeb M. Community-acquired pneumonia in adults. NEJM Evid. 2025;4(12). doi:10.1056/EVIDra2500170

  • Summary: This review provides an overview of adult community-acquired pneumonia in the United States, detailing its substantial clinical burden, underlying pathophysiology, common microbial causes, diagnostic and microbiologic testing considerations, recommended pharmacologic management, and the long-term adverse health outcomes associated with the disease.

Aanensen DM, Okeke IN, Donado-Godoy P, Egyir B, Lingegowda RK, Sia S; on behalf of the NIHR Global Health Research Unit on Genomic Surveillance of AMR. The genomic surveillance gap: averting the antimicrobial resistance pandemic requires global equity and action. Lancet Infect Dis. 2025. doi:10.1016/S1473-3099(25)00723-6

  • Summary: This commentary argues that the unprecedented global genomic sequencing capacity built during the COVID-19 pandemic is now being underutilized, and calls for redirecting this capability toward the escalating antimicrobial resistance crisis, which causes nearly 5 million deaths each year and requires sustained, coordinated genomic surveillance to detect and mitigate emerging threats.

Anglemyer A, Srinivas A, McNeill A, Allen C, Cooper H, Morgan J, et al. Large Reductions in Invasive Pneumococcal Disease and Related Morbidities Among Children in New Zealand After Change from PCV10 to PCV13. J Infect Dis. 2025; jiaf587. doi:10.1093/infdis/jiaf587

  • Summary: This study shows that reintroducing PCV13 into New Zealand’s immunization program in 2022 led to a reduction in invasive pneumococcal disease in children, reversing the rising incidence—particularly from serotype 19A—that would have been expected if PCV10 had remained in use, emphasizing the value of adapting vaccine strategies based on real-time epidemiology.

Hall CW, Waglechner N, Choi E, Aftanas P, Katz K, Vermeiren C, et al. Evaluation of phenotypic and genotypic susceptibility testing methods for newer β-lactam/β-lactamase inhibitor combinations in multidrug resistant Pseudomonas aeruginosa. J Infect Dis. 2025; jiaf585. doi:10.1093/infdis/jiaf585

  • Summary: This study evaluated commercial susceptibility testing panels and genomic prediction tools for newer β-lactam/β-lactamase inhibitor combinations against multidrug-resistant Pseudomonas aeruginosa, finding that Sensititre performed reliably while the Phoenix panel frequently misclassified resistance, and that genotypic tools failed to predict many resistant phenotypes due to the rarity of identifiable β-lactamase genes—highlighting the ongoing need for accurate phenotypic testing and deeper understanding of resistance mechanisms.

Lenz S, Biswas S, Terry I, Tran-Basha L, Lyons AK, Mazumdar T, et al. Detection of carbapenem-resistant bacteria in skilled nursing facility wastewater. J Infect Dis. 2025; jiaf534. doi:10.1093/infdis/jiaf534

  • Summary: This study demonstrates that wastewater surveillance in skilled nursing facilities can detect a diverse community of carbapenem-resistant bacteria, including clinically important and environmental species, and shows that combining culture, PCR, and whole-genome sequencing provides a reliable approach for identifying carbapenemase genes—offering proof-of-concept for wastewater-based early detection of antimicrobial resistance threats in healthcare settings.

Astorga G, Bloomfield SJ, Palau R, Janecko N, de Oliveira Martins L, Singh D, et al. A multi-isolate genomic approach identifies diverse Escherichia coli contamination and antimicrobial resistance carriage on retail foods. Microb Genom. 2025;11(10):001549. doi:10.1099/mgen.0.001549

  • Summary: This study used whole-genome sequencing of more than one thousand E. coli isolates from retail chicken, leafy greens, pork, prawns, and salmon in Norfolk, UK. The results showed extremely high genetic diversity, with hundreds of sequence types and many samples containing multiple unrelated strains. Many isolates carried antimicrobial resistance genes, and some contained virulence profiles consistent with extraintestinal pathogenic E. coli. Traditional approaches that simply count E. coli on food would have missed this hidden diversity and the potential risks it represents. The findings show that testing multiple isolates per sample and applying whole-genome sequencing provides a much more complete picture of contamination and consumer risk.

Williams A, Coombs G, Bell J, Daley D, Mowlaboccus S, Bryant P, et al. Australian Group on Antimicrobial Resistance (AGAR) surveillance outcome programs – bloodstream infections and antimicrobial resistance patterns in Australian children and adolescents, January 2022–December 2023. Commun Dis Intell. 2025 Nov 18; doi:10.33321/cdi.2025.49.052

  • Summary: This 2022–2023 Australian pediatric surveillance report found that most bloodstream infections were community-onset and occurred in infants under 12 months. Among gram-negative bacteria, Enterobacterales predominated, with notable resistance including rising ciprofloxacin resistance driven by Salmonella Typhi. Thirteen percent were ESBL producers and nearly one in five were multidrug resistant. Methicillin-resistant Staphylococcus aureus made up 14 percent of S. aureus isolates, and all highly resistant enterococcal isolates were E. faecium. Overall resistance patterns were similar to prior years, with small increases highlighting the need for continued monitoring.

Fraser AJ, Parry CM, Larru B, Case L, Ball K, Duggan C, et al. A 46-week outbreak of ertapenem-resistant, non-carbapenemase encoding Klebsiella pneumoniae ST45 in a paediatric cardiac unit involving shared equipment, United Kingdom, April 2022 to February 2023. Euro Surveill. 2025;30(43):pii=2500133. doi:10.2807/1560-7917.ES.2025.30.43.2500133

  • Summary: This study investigates a prolonged outbreak of multidrug-resistant Klebsiella pneumoniae in a UK children’s hospital, showing through genomic analysis that transmission occurred within the hospital—likely via shared equipment—and highlighting the need for strong infection prevention measures, awareness of atypical resistance mechanisms, and the value of whole genome sequencing in accurately defining related cases and guiding outbreak control.

Morgan DJ, AlShanqeeti S, Coffey KC, Baghdadi JD, Goodman KE, Holman JL, et al. Using generative artificial intelligence to identify central line-associated bloodstream infections. Clin Infect Dis. 2025 Nov 19;ciaf636. doi:10.1093/cid/ciaf636

  • Summary: This study evaluated generative AI for identifying central line–associated bloodstream infections (CLABSIs) across 11 US hospitals, finding that AI-assisted review was at least as accurate as traditional expert review, faster, less variable across sites, and preferred by infection control staff, suggesting that AI could streamline and improve CLABSI surveillance and reporting.

Cheng HCR, Teixeira D. Unpacking the spread of pathogens. Nat Rev Microbiol. 2025 Nov 17; doi:10.1038/s41579-025-01264-w

  • Summary: This Genome Watch highlights new advances in genomic epidemiology that allow high-resolution, scalable reconstruction of transmission events, improving our ability to track pathogen spread in increasingly complex settings.

Chosidow A, Maakaroun-Vermesse Z, Ok V, Delecroix C, Le Roux P, Dommergues MA, et al. Post-COVID-19 resurgence of Mycoplasma pneumoniae infections in French children (ORIGAMI): a retrospective and prospective multicentre cohort study. Lancet Infect Dis. 2025 Nov 19; doi:10.1016/S1473-3099(25)00598-5

  • Summary: A nationwide French study of 969 hospitalized children during the 2023–2024 Mycoplasma pneumoniae resurgence found that most had pneumonia and were treated with macrolides, macrolide resistance remained rare, and although severe cases were uncommon, older children, those with asthma or other comorbidities, and those with erythema multiforme had significantly higher risk of PICU admission, underscoring the substantial clinical burden and need for continued surveillance and targeted management.

Egyir B, Tagoe R, Dayie NTKD, Bentum J, Owusu-Nyantakyi C, Baka DK, et al. Global high-risk clones and multidrug-resistant serotype strains of Pseudomonas aeruginosa from surgical site infections in low-resource settings. Microbiol Spectr. 2025 Oct 30; doi:10.1128/spectrum.00314-25

  • Summary: Whole-genome sequencing of Pseudomonas aeruginosa from surgical site infections in Ghana revealed extensive genetic diversity, multiple high-risk and newly emerging clones, notable resistance to key antibiotics—including multidrug resistance—and the presence of important virulence genes, highlighting the urgent need for strengthened genomic surveillance, infection prevention, and antimicrobial stewardship in low-resource healthcare settings.

Vieni C, Rothstein T, Johnson S, Schuetz AN, Norgan A, Patel R. Whole genome sequence analysis of Helicobacter pylori isolates reveals incomplete characterization of antimicrobial resistance mechanisms. iScience. 2025 Nov 17; doi:10.1016/j.isci.2025.114077

  • Summary: A nationwide genomic analysis of 530 Helicobacter pylori isolates in the US shows extensive genetic diversity without geographic clustering, confirms that clarithromycin and levofloxacin resistance is driven by known 23S rRNA and GyrA mutations, and reveals that resistance to amoxicillin, metronidazole, and rifampin lacks clear genetic markers, underscoring the need for deeper investigation into the mechanisms of antimicrobial resistance in this pathogen.

Cillóniz C, Fally M, Evans S, Dy-Agrag G, the Pneumo-Strategy group. The pneumonia challenge: time to end the global neglect. Lancet Glob Health. 2025 Nov 11; doi:10.1016/S2214-109X(25)00374-2

  • Summary: This article highlights pneumonia as a leading yet largely neglected infectious killer—claiming nearly 2 million preventable deaths each year, particularly among children and older adults in the poorest regions—driven by inequities in nutrition, vaccination, diagnostics, oxygen access, and health care, and calls for urgently applying recent global health advances, such as improved vaccines, genomic surveillance, diagnostics, and digital health innovations, to reduce pneumonia mortality and ensure equitable protection and care worldwide.

Contou D, Painvin B, Daubin D, Orieux A, Pirollet H, Cour M, et al. Hemodynamic and neurological presentations of invasive meningococcal disease in adults: a nationwide study across 100+ French ICUs (The RETRO-MENINGO study). Intensive Care Med. 2025 Aug 12; doi:10.1007/s00134-025-08043-4

Pîrîianu-Masgras RB, Mebazaa A, Savarese G, Stoica E, Geavlete O, Ambrosy AP, et al. Infective endocarditis complicated by shock: a systematic review and meta-analysis. Heart Fail Rev. 2025 Aug 30; doi:10.1007/s10741-025-10556-5

  • Summary: This systematic review and meta-analysis of seven observational studies (2015–2025) shows that infective endocarditis complicated by septic or cardiogenic shock carries very high mortality, with pooled in-hospital mortality over 60% and an almost six-fold higher death risk compared with IE without shock. Staphylococcus aureus is the most common pathogen, and shock is often accompanied by acute kidney injury, neurological complications, and multiorgan failure. Early valve surgery is associated with improved survival—especially in cardiogenic shock—highlighting the need for rapid recognition, immediate antimicrobial therapy, hemodynamic support, and timely surgical intervention.

La P, Korn R, Cox PB, Goel D, Jabbour JF, Westgeest AC, et al. Female sex and mortality in patients with Gram-negative bacteremia: a systematic review and meta-analysis. JAMA Netw Open. 2025 Nov 13; doi:10.1001/jamanetworkopen.2025.43552

  • Summary: This systematic review and meta-analysis of more than 16,000 adults with gram-negative bloodstream infections found that female sex was not associated with increased mortality after statistical adjustment, contrasting with the higher mortality risk observed in women with Staphylococcus aureus bloodstream infections and underscoring the need to understand why sex-specific differences exist in SA-BSI but not GN-BSI.

Zuza AM, Pearse O, Domman DB, Dyson ZA, Kawaza K, Musicha P, et al. Temporal genome dynamics of ST39 Klebsiella pneumoniae in a neonatal unit in Blantyre, Malawi. bioRxiv. 2025 Nov 9. doi:10.1101/2025.11.06.25339690

  • Summary: This study of Klebsiella pneumoniae ST39 circulating for two decades in a Malawian hospital shows that the neonatal outbreak clone carried multiple variable genomic regions—largely driven by bacteriophage activity—highlighting the substantial genome plasticity that enables ST39 to acquire new traits, adapt to the hospital environment, and potentially increase virulence and antimicrobial resistance.

Mycobacterial Infections

Greenan-Barrett J, Mendelsohn SC, Scriba TJ, Noursadeghi M, Gupta RK. Single-gene transcripts for subclinical tuberculosis: an individual participant data meta-analysis. Lancet Microbe. 2025 Oct 2;6(11):101186; doi:10.1016/j.lanmic.2025.101186

  • Summary: In this meta-analysis of 6544 samples, several single-gene blood RNA transcripts performed as well as multi-gene signatures for detecting subclinical tuberculosis, showing consistent accuracy across settings, and although none met the WHO progression test target, they outperformed interferon-γ release assays (IGRAs) in high-burden settings and offered complementary value to IGRAs in low-burden settings for guiding preventive treatment strategies.

Zhang Y, Li D, Liu J, Jiang Y, Shen X, Xu B. Association between pre-diagnostic fluoroquinolone exposure and possible acquired fluoroquinolone resistance in Mycobacterium tuberculosis in Shanghai: an EHR-based case-control study using whole-genome sequencing. J Infect. 2025;91(5):106648; doi:10.1016/j.jinf.2025.106648

  • Summary: In a Shanghai case-control study of 3496 TB patients, fluoroquinolone resistance—mostly acquired—was strongly associated with pre-diagnostic FQ exposure in a clear dose-response pattern, with most FQ prescriptions originating from non-TB hospitals for respiratory illnesses, highlighting the urgent need for more judicious FQ use to prevent acquired resistance.

Nguyen HT, Vo LNQ, Codlin AJ, Forse R, Wingfield T, Annerstedt KS, et al. Diagnostic accuracy of the STANDARD F TB-Feron FIA assay for tuberculosis infection in Vietnam: a cross-sectional study. Clin Infect Dis. 2025 Nov 26; doi:10.1093/cid/ciaf561

  • Summary: In a cross-sectional study of 345 participants in Vietnam, the near–point-of-care STANDARD F TB-Feron assay demonstrated high sensitivity but modest specificity compared with QFT-Plus for detecting TB infection, showing good agreement and reproducibility and suggesting its potential as an accessible diagnostic tool despite specificity limitations.

Wu Z, Yan L, Lai X, Yang J, Liang J, Ma X, et al. Diagnostic accuracy of a novel point-of-care tongue swab assay for pulmonary tuberculosis: a multicenter prospective study. Clin Microbiol Infect. 2025 Nov 15; doi:10.1016/j.cmi.2025.11.010

  • Summary: In a multicenter study of 594 symptomatic participants, the MiniDock point-of-care molecular test showed high accuracy on sputum and moderate but load-dependent sensitivity on tongue swabs, offering a rapid, reliable, and non-invasive TB diagnostic option that is especially useful when sputum cannot be obtained.

Raaijmakers J, Aarnoutse R, te Brake L, Stemkens R, Wertheim H, Hoefsloot W, et al. Enhanced antimycobacterial efficacy of simulated inhaled clofazimine versus oral clofazimine in combination with azithromycin and ethambutol in a hollow-fiber system. J Antimicrob Chemother. 2025 Nov 10; doi:10.1093/jac/dkaf402

  • Summary: In a hollow-fiber model simulating clinical drug exposures, inhaled clofazimine combined with azithromycin and ethambutol produced faster intracellular and extracellular killing of Mycobacterium avium and reduced macrolide resistance compared to oral clofazimine, supporting the need for clinical trials of inhaled therapy.

Murrill MT, Velásquez GE, Szumowski JD, Phillips A, Kim A, Yazdany J, et al. Tuberculosis infection screening recommendations for targeted immunotherapies: comparison of U.S. prescribing information, clinical resources and quality measures. Clin Infect Dis. 2025 Nov 19; doi:10.1093/cid/ciaf628

  • Summary: A review of FDA prescribing information, TB clinical resources, and quality measures found that although all TNF inhibitors consistently include tuberculosis screening recommendations, only 13% of 269 targeted immunotherapies do so, with highly variable guidance for newer agents such as IL-6 and JAK inhibitors, creating discordant recommendations that may hinder effective TB preventive care and highlight the need for harmonized, up-to-date screening guidance.

Heo W, Wang Q, Choi S, Shin J, Park SJ, Park S, et al. Lab-in-a-cartridge for real-time detection of tuberculosis via precise measurement of urinary lipoarabinomannan. Nat Commun. 2025 Nov 21;16:10299. doi:10.1038/s41467-025-65217-w

  • Summary: A novel lab-in-a-cartridge system enables portable, on-site urine LAM detection through pumpless fluid handling, magnetic enrichment, and amplified colorimetric readout, achieving 0.01 pg/mL sensitivity in 40 minutes and correctly identifying TB in clinical samples with 92% sensitivity and 88% specificity, offering a promising tool for decentralized TB diagnosis in resource-limited settings.

Wang C, Marciano BE, Harris AJ, Johnston AM, Apaydin Arikan E, Bayer DK, et al. IL12RB1 deficiency appearing in North America: expanding the clinical phenotypes. Clin Infect Dis. 2025 Nov 18; doi:10.1093/cid/ciaf637

  • Summary: IL12RB1 deficiency, the most common genetic cause of Mendelian susceptibility to mycobacterial disease, typically presents as disseminated BCG infection worldwide but in North America—where BCG is not used—it more often appears as diverse bacterial and fungal infections, underscoring region-specific and frequently overlooked clinical manifestations.

Fungal Infections

Walsh TJ, Sicignano D, Mastropietro M, Lovelace B, Coleman CI. Aspergillosis-attributable mortality in the United States: analysis of death certificate data. Clin Infect Dis. 2025 Nov 24; doi:10.1093/cid/ciaf653

  • Summary: Analysis of 2018–2024 US death certificate data identified 7063 aspergillosis-attributable deaths, showing rising mortality in recent years, highest rates in older adults and males, and substantial geographic variation, with findings informing efforts to better characterize and address aspergillosis burden.

Yeoh DK, Butters C, Clark JE, Slavin MA, McMullan BJ, Haeusler GM, et al. Invasive mould infection in children – advances made or obstacles remaining? Clin Microbiol Infect. Published 27 November 2025. doi:10.1016/j.cmi.2025.11.023

  • Summary: Invasive mould infections in immunocompromised children remain difficult to diagnose and treat despite advances in imaging, biomarkers, molecular assays, and new antifungals, underscoring the need for more paediatric data to guide clinical use.

Wu J, Zhang L, He X, Xu S, Yang J, Xing X. Coil embolization of pulmonary artery pseudoaneurysms in mucormycosis: efficacy and bronchial erosion complication. Clin Microbiol Infect. Published 21 November 2025. doi:10.1016/j.cmi.2025.11.014

  • Summary: Pulmonary mucormycosis can cause life-threatening hemoptysis through pulmonary artery pseudoaneurysms, and while surgery is often not feasible, this case series shows that endovascular embolization offers a viable minimally invasive treatment with an 80% cure rate.

Huang W, Lu D, Lu Z, Luo X. Chronic wound infection caused by Phialophora americana. Clin Microbiol Infect. Published 21 November 2025. doi:10.1016/j.cmi.2025.11.012

  • Summary: An 82-year-old immunosuppressed man on long-term glucocorticoids developed chronic, progressively worsening calf ulcers after a tomato leaf scratch, presenting with deep, foul-smelling, nonhealing wounds suggestive of severe secondary infection.

Verma S, Tilak R, Singh G, Singh S, Kumari A, Rudramurthy SM, et al. Multicentre investigation of Wickerhamomyces anomalus fungemia in India: emerging resistance and mechanistic insights. J Antimicrob Chemother. Published 24 November 2025. doi:10.1093/jac/dkaf420

  • Summary: A multicenter study of 70 Wickerhamomyces anomalus isolates from Indian hospitals found widespread fluconazole non-wild-type resistance, high neonatal fungemia and mortality, and resistance mechanisms involving ERG11 mutations, efflux pump overexpression, biofilm formation, and clonal transmission.

Eichenberger EM, Pouch S. Candida. J Heart Lung Transplant. Published online 1 October 2025;10100401. doi:10.1016/j.jhlto.2025.100401

  • Summary: Invasive candidiasis in thoracic organ transplant recipients presents in multiple severe forms and is challenging to diagnose and manage, with rising concerns about antifungal resistance in this vulnerable population.

Elmasry WG, Abdelbaky AM, Awad AHA. Management of invasive candidiasis in the ICU: challenges and advances. Med Int. Published online 24 October 2025;79. doi:10.3892/mi.2025.278

  • Summary: Invasive candidiasis remains a major cause of morbidity and mortality in ICU patients due to delayed diagnosis, rising multidrug-resistant Candida, and management difficulties, but advances in rapid molecular diagnostics, new antifungals, stewardship strategies, and updated guidelines are improving early detection and treatment while highlighting the need for continued research.

Phillips B, Most ZM, Connors B, Jackson P, Sebert ME. Multiyear environmental surveillance in a pediatric teaching hospital: association between airborne mold spores and invasive mold infections. Infect Control Hosp Epidemiol. 2025;46(11):1119–26. doi:10.1017/ice.2025.10264

  • Summary: A five-year study of airborne fungal load monitoring in a pediatric hospital found no overall facility-wide link to invasive mold infections, but on hematology/oncology units even small increases in local airborne fungal counts—especially Aspergillus—were strongly associated with higher infection rates, suggesting that targeted indoor AFL surveillance may help identify periods of elevated IMI risk for vulnerable patients.

Hindler JA, Schuetz AN. CLSI AST news update. CLSI AST News Updates. 2025;11(1)

  • Summary: In this issue (pages 5 to 8) there is a review on Candida auris from the laboratory aspect. It includes a useful table of methods that can be reliably used to detect C. auris, as well as discussion on susceptibility testing for this yeast.

Diagnostics

Nguyen Van JC, Pilmis B, El Helali N, Azria E, Bruel C, Ganansia O, et al. Implementing POCT in infectious diseases. Clin Infect Dis. 2025 Nov 27; doi:10.1093/cid/ciaf650

  • Summary: This viewpoint outlines operational lessons and a strategic roadmap for implementing nucleic acid–based point-of-care testing across healthcare settings, emphasizing barriers, facilitators, stewardship-aligned integration in critical care and outpatient systems, and core principles such as equity, sustainability, and clinical alignment to support scalable diagnostic deployment.

Podkowik M, Tillman A, Takats C, Carion H, Putzel G, McWilliams J, et al. CRISPR-Cas–associated SCCmec variants in methicillin-resistant Staphylococcus aureus evade rapid diagnostic detection. J Infect Dis. 2025 Nov 19; doi:10.1093/infdis/jiaf575

  • Summary: This study identifies CRISPR-Cas–associated SCCmec variants in clonal complex 5 MRSA that evade detection by rapid molecular assays targeting SCCmec or the SCCmec–orfX junction, accounting for 2% of screened isolates, leading to false-negative results, highlighting mecA instability, healthcare-associated circulation, and a significant emerging threat to diagnostic accuracy.

Zhang Y, Chow EPF, Zhang L, Fairley CK, Ong JJ. Comparison of the performance and costs of testing algorithms using rapid diagnostic tests for detection and treatment of syphilis among pregnant individuals and men who have sex with men: a modelling study. Lancet Infect Dis. 2025 Nov 21; doi:10.1016/S1473-3099(25)00588-2

  • Summary: This modeling study finds that no single rapid diagnostic testing algorithm is optimal for syphilis across all settings, with treponemal-only RDTs remaining cost-efficient for antenatal screening and dual treponemal/non-treponemal RDTs—standard or modified—better suited for higher-risk groups such as MSM due to fewer missed infections despite increased overtreatment.

Zhong Y, Hope W, Buchan I, Velluva A, Gerada A, Rosato C, Green PL, Howard A. Machine learning for personalized antimicrobial susceptibility breakpoints (Adaptive clinical breakpoint interpretation). J Antimicrob Chemother. 2025 Nov 12; dkaf419. doi:10.1093/jac/dkaf419

  • Summary: Machine-learning models with modest discrimination (AUC 0.62) were able to correctly guide EUCAST-aligned aminopenicillin dosing for most Enterobacterales bacteriuria and bacteraemia cases, supporting a proof-of-concept that diagnosis-prediction models could enable personalized breakpoint interpretation in clinical microbiology.

Ginsburg AS, McCollum ED, Kwarteng-Owusu S. Paediatric pneumonia: a call for point-of-care diagnostics and prognostics. Lancet Glob Health. 2025 Nov 11;13(12):e2002–e2003. doi:10.1016/S2214-109X(25)00371-7

  • Summary: Paediatric pneumonia remains the leading infectious cause of child mortality, and in low-resource settings the lack of accurate, point-of-care diagnostics leads to both missed and overdiagnosed cases, underscoring the need for validated, child-friendly tools—such as lung ultrasound, acoustic technologies, and emerging biomarker or AI-based tests—to improve diagnosis, severity assessment, and antibiotic stewardship.

Kupferwasser DK, Kang AY, Bolaris M, Huse H, Chen L, Miller L. Diagnostic stewardship cutoffs for urinalysis results prior to performing a urine culture: analysis of data from a healthcare system. Infection Control Hosp Epidemiol. 2025 Sep 16;46(11):1097–1104. doi:10.1017/ice.2025.10265

  • Summary: In a large retrospective study of nearly 81,000 paired urinalyses and urine cultures, microscopic white blood cell count was the most accurate urinalysis parameter for predicting true uropathogens, outperforming leukocyte esterase, nitrite, bacteria, squamous epithelial cells, and all parameter combinations, supporting its use as the primary screening tool in reflex culture stewardship algorithms.

Improving Clinical Trials

Hamasaki T, He Y, Wu Q, Howard-Anderson J, Boucher HW, Doernberg SB, et al. A patient-centric paradigm and tool for clinical research: the DOOR is open. Antimicrob Agents Chemother. 2025 Nov 24; doi:10.1128/aac.01478-25

  • Summary: This article describes how the desirability of outcome ranking (DOOR) framework addresses limitations of traditional trial analyses by integrating multiple benefits and harms into a single patient-centered measure, and provides a recommended statistical analysis plan and online tool to support designing and interpreting DOOR-based clinical studies.

Mao L, Tian L, Huang B, Richardson PG, Ludmir EB, Hughes MD, et al. Evaluating treatment effects with patient-response–related outcomes in comparative clinical trials. NEJM Evid. 2025 Nov 25;4(12). doi:10.1056/EVIDctw2400349

  • Summary: This workshop introduces a new method for analyzing time to response and duration of response in clinical trials, using data from JAVELIN Renal-101 to show how it can better characterize treatment effects than traditional response-rate metrics.

Jackson H, Sauser J, van Werkhoven CH, Harbarth S, de Kraker MEA. Benefits of group sequential design and sample size re-estimation for randomised controlled trials evaluating the prevention of ventilator-associated pneumonia: a simulation study informed by real world data. BMC Med Res Methodol. 2025 Nov 12;25:254. doi:10.1186/s12874-025-02681-4

  • Summary: Simulations based on HONEST-PREPS data show that group sequential and sample-size–re-estimation designs can reduce expected sample sizes by roughly 9–12% versus fixed RCTs when testing VAP prevention strategies, making these adaptive approaches more efficient and better powered for pathogen-specific interventions.

Carroll K, Hemkens LG, Hatswell AJ, Kristunas C, Emperador D, Mitchell A, et al. Agreement of treatment effects in decentralised trials versus traditional trials: meta-epidemiological study. BMJ. 2025 Nov 18;391:e084307. doi:10.1136/bmj-2025-084307

  • Summary: Across 51 decentralised and 86 non-decentralised trials addressing 11 clinical questions, treatment effects were statistically consistent with no systematic bias, indicating that decentralised trials yield similar effect estimates while enabling larger, more contemporary studies.

Lee CJ, Gross CP, Miller JE. Physical accessibility of medicines in countries hosting trials for FDA approvals. JAMA Intern Med. 2025 Nov 17; doi:10.1001/jamainternmed.2025.6060

  • Summary: Only 24% of FDA-approved medicines (2015–2018) were physically accessible in all trial-participating countries within 5 years, with high-income countries—especially Western Europe—showing far better access than LMICs, which saw no improvement over time, highlighting persistent global inequities and exploitation concerns.

Burry L, Sharshar T, Poole D. When the sirens of statistics eclipse the clinical question. Intensive Care Med. 2025 Nov 13; doi:10.1007/s00134-025-08202-7

  • Summary: Hyperactive ICU delirium remains difficult to treat, and although the 4D RCT reported that dexmedetomidine improved agitation control in non-intubated patients, its primary joint outcome was statistically significant yet clinically uninterpretable, with no effect on delirium resolution or intubation, raising concerns about early trial termination and emphasizing the need for clinically meaningful endpoints.

Corriero A, Soloperto R, Giglio M, Salvagno M, Trerotoli P, Grasso S, et al. Probiotics to reduce ventilator-associated pneumonia in adults with acute non-anoxic brain injury: study protocol for a double-blind multicenter randomized international clinical trial (PROACT). Trials. 2025 Nov 10;26:484. doi:10.1186/s13063-025-09230-w

  • Summary: The PROACT trial will test whether twice-daily probiotic prophylaxis can reduce ventilator-associated pneumonia in mechanically ventilated adults with acute brain injury, excluding those with early pulmonary infection, using a randomized double-blind design with VAP incidence as the primary endpoint and secondary outcomes including infections, mortality, and ICU resource use.

Das S, Ahmed A, Capurro O, Carr MJ, Barerro Castedo F, Fridkin SK, et al. Protocol for a multicenter, cluster-randomized, stepped-wedge, implementation trial of a prehospital sepsis protocol. Trials. 2025 Nov 11;26:491. doi:10.1186/s13063-025-09172-3

  • Summary: This stepped-wedge EMS trial will assess whether implementing a prehospital sepsis screening and early-notification protocol reduces time to first antibiotics in true sepsis cases while monitoring antibiotic exposure in non-septic patients to evaluate safety.

Bodilsen J, Leeflang MMG, Rodriguez Bano J, Wolkewitz M, Leibovici L. Editorial Note: Launch of the “Reviews on Research Methods” Collection. Clin Microbiol Infect. 2025 Nov 13; doi:10.1016/j.cmi.2025.11.006

  • Summary: This announcement introduces the new Clin Microbiol Infect collection “Reviews on Research Methods,” which provides expert guidance on methodology topics such as study design, bias, confounding, and epidemiologic approaches.

General Interest

Wee LE, Tan WZ, Chow JY, Lim JT, Chiew C, Chia PY, et al. Neurological events associated with acute dengue infection. JAMA Neurol. 2025 Nov 24; doi:10.1001/jamaneurol.2025.4608

  • Summary: This large population-based cohort study from Singapore found that dengue virus infection was associated with significantly increased odds of several acute neurological events within 30–90 days—such as memory loss and movement or other neurological disorders—but with a modest overall excess burden (<1 extra event per 100 cases), with risks concentrated in adults aged ≥60 years and during DENV-3 transmission.

Durbin AP, Van Wesenbeeck L, Pierce KK, Herrera-Taracena G, Ebone L, Buelens A, et al. Daily Mosnodenvir as dengue prophylaxis in a controlled human infection model. N Engl J Med. 2025 Nov 26;393:2107–18. doi:10.1056/NEJMoa2500179

Bifulco M, Di Zazzo E, Pagano C, Orsini D, Affinito A. Syphilis transmission: contagion of bodies and words. J Infect Dis. 2025 Nov 14; doi:10.1093/infdis/jiaf576

  • Summary: This abstract reviews the origins, social impact, and treatments of syphilis, showing how historical epidemics leave lasting cultural and linguistic imprints such as Neapolitan folk sayings.

Schmitt B, Cesario T, Savoia M. Infectious disease risk management in body donation programs. J Infect Dis. 2025 Nov 14; doi:10.1093/infdis/jiaf579

  • Summary: This letter responds to a recent article urging expanded whole-body donation eligibility for people with HIV or viral hepatitis, noting agreement on donor dignity while emphasizing that the University of California review committee continues to reassess risks and safety considerations tied to transmissibility and current treatments.

Chalmers JD, Haworth CS, Flume P, et al. European Respiratory Society clinical practice guideline for the management of adult bronchiectasis. Eur Respir J. 2025;2501126. doi:10.1183/13993003.01126-2025

  • Summary: International ERS guidelines recommend airway clearance, pulmonary rehabilitation, long-term macrolides, and long-term inhaled antibiotics for high-risk adults with bronchiectasis, along with targeted use of eradication and mucoactive therapies, while advising against routine non-macrolide oral antibiotics or inhaled corticosteroids.

McLean W, Port D, Sims D, Curtis O. Group C beta haemolytic Streptococcus causing necrotising pneumonia complicated with a pyopneumothorax. Case Rep Pulmonol. 2025 Oct 31; doi:10.1155/crpu/8885401

  • Summary: A rare case of invasive Group C β-haemolytic Streptococcus pneumonia in a healthy young man caused pyopneumothorax, multiorgan failure, and need for bilateral VATS, highlighting the severity, possible zoonotic links, and male predominance of reported cases.

Suzuki K, Otsuka H. Lemierre’s syndrome. JMA J. 2025 Oct 15;8(4):1423–4. doi:10.31662/jmaj.2025-0207

  • Summary: A healthy 23-year-old man with fever and sore throat rapidly deteriorated into shock and respiratory failure, with imaging showing multiple pulmonary masses concerning for metastatic disease, ultimately suggesting Lemierre’s syndrome from Fusobacterium necrophorum septic thrombophlebitis with septic emboli.

Kontoyiannis DP, Lewis RE, Walsh TJ, Cornely OA, Rolston KV, Pizzo PA, et al. On the shoulders of a giant: an appraisal of the legacy of Dr Gerald P Bodey to infectious diseases. Clin Microbiol Infect. 2025 Nov 13; doi:10.1016/j.cmi.2025.11.008

  • Summary: This review highlights Gerald P. Bodey’s transformative contributions to infection management in immunocompromised cancer patients, detailing seven principles—from neutrophil-based risk assessment to empirical antibiotics, prophylaxis, and recognition of fungal threats—that established modern standards of care and continue to guide evolving oncology practice.

Aghajani A, Naderi Beni A, Vasezade S. Optic disc complication of orbital abscess. JAMA Ophthalmol. 2025 Nov 13; doi:10.1001/jamaophthalmol.2025.4499

  • Summary: Visual morbidity from orbital abscess is mainly driven by optic nerve damage from compression, inflammation, or ischemia, and although complications of orbital cellulitis and subperiosteal abscesses are well known, complete vision loss in this context appears to be rarely reported.

Alpert E, Silk H, Simon L. Dental caries in adults. JAMA. 2025 Nov 12; doi:10.1001/jama.2025.19029

  • Summary: Dental caries results from enamel demineralization caused by bacterial acid production from dietary carbohydrates, with plaque, Streptococcus mutans, sugar intake, poor oral hygiene, xerostomia, and substance use increasing risk, while fluoride provides protection and disparities in access to care drive unequal burden.

Mody L, Advani SD, Ashraf MS, Bartlett AH, Bradley SF, Burdsall DP, et al. Multisociety guidance for infection prevention and control in nursing homes. Infection Control & Hospital Epidemiology. 2025;46(11):1069–96. doi:10.1017/ice.2025.10252

  • Summary: Multisociety guidance offers recommendations to strengthen infection prevention and control in U.S. nursing homes, addressing leadership, staffing, hand hygiene, precautions, outbreak preparedness, environmental cleaning, training, and regulatory considerations amid rising acuity, multidrug-resistant organisms, and emerging pathogens.
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