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Issue: Newsletter 13 | February 1, 2026

Randomised Controlled Trials

Citation of Articles PICO Main Results Risk of Bias
Solomon T, Hooper C, Easton A, Rosala-Hallas A, Facer B, Moore P, et al. Safety and efficacy of adjunct dexamethasone in adults with herpes simplex virus encephalitis in the UK (DexEnceph): a multicentre, observer-blind, randomised, phase 3, controlled trial. Lancet Neurol. 2026 Feb;25(2):136–146. doi:10.1016/S1474-4422(25)00454-5 P: 94 adults with HSV encephalitis (aged ≥16 years; 47 per group; confirmed HSV-1 or HSV-2 PCR in CSF), with 81 included in modified intention-to-treat analysis
I: Intravenous dexamethasone 10 mg/kg four times daily for 4 days plus intravenous aciclovir 10 mg/kg three times daily for ≥14 days
C: Intravenous aciclovir 10 mg/kg three times daily for ≥14 days alone
O: Verbal memory score at 26 weeks (WMS-IV auditory memory index); safety and adverse events 		Adjunct dexamethasone did not significantly improve verbal memory at 26 weeks compared with aciclovir alone (mean score 71 vs 69; adjusted difference 1.77, 95% CI –9.57 to 13.12; p=0.76). Adverse events were similar between groups, occurring in 40% of the dexamethasone group and 38% of the control group. Serious adverse events were uncommon and comparable, including seizures requiring readmission (2% in each group) and thrombotic events observed only in the dexamethasone group (deep vein thrombosis 2%, pulmonary embolism 2%). No treatment-related deaths occurred, indicating a satisfactory safety profile but no efficacy benefit on cognitive outcomes. Moderate risk: The observer-blind design with masked outcome assessors and statisticians reduces detection bias, but treatment allocation was not fully blinded, introducing potential performance bias. The modest sample size and early withdrawals (13% withdrew consent or were lost to follow-up) limit statistical power and may affect generalizability. Delayed initiation of dexamethasone (median 7 days after admission) could have diluted treatment effects, potentially biasing results toward null efficacy.
Louie T, Ribble W, Boccumini L, Johnson K, De Groote MA, Day J, et al. Safety and efficacy of CRS3123 in adults with a primary episode or first recurrence of Clostridioides difficile infection: a phase 2, randomised, double-blind, multicentre, vancomycin-controlled study. Lancet Infect Dis. 2026 Jan 22; doi:10.1016/S1473-3099(25)00721-2 P: 43 adults with Clostridioides difficile infection (mean age 58.4 years; 77% female; 72% primary episode, 28% first recurrence), recruited across 14 sites in the USA and Canada
I: CRS3123 200 mg orally twice daily for 10 days or CRS3123 400 mg orally twice daily for 10 days
C: Oral vancomycin 125 mg four times daily for 10 days
O: Clinical cure at test-of-cure visit (day 12–15); CDI recurrence at days 40 and 70; safety and adverse events 		Clinical cure at test-of-cure was high and comparable across groups (93% with CRS3123 200 mg, 100% with CRS3123 400 mg, and 93% with vancomycin), with no clinical failures observed. Treatment-emergent adverse events were mild to moderate and similar between groups; drug-related adverse events occurred only in CRS3123 recipients and were grade 1–2, while the only serious adverse event (pneumonia) occurred in the vancomycin group and was unrelated to treatment. CDI recurrence through day 40 was lower with CRS3123 (0% with 200 mg; 7% with 400 mg) compared with vancomycin (23%), with one additional recurrence at day 70 in the CRS3123 400 mg group, suggesting comparable short-term efficacy and a potential reduction in recurrence. Moderate risk: The randomized, double-blind, active-controlled design with stratification by CDI history reduces selection, performance, and detection bias. However, the small sample size limits statistical power and precision of efficacy estimates, particularly for recurrence outcomes. Missing data leading to indeterminate responses at test-of-cure and short follow-up for recurrence further constrain robustness and generalizability.
De Coster I, AbdelGhany M, Sarakinou E, Fineschi C, Marchetti E, La Gaetana R, et al. Safety and immunogenicity of a conjugate vaccine candidate against Salmonella enterica serovars Typhi and Paratyphi A in healthy adults in Europe: a phase 1 randomised controlled trial. Lancet Infect Dis. 2026 Jan 23; doi:10.1016/S1473-3099(25)00730-3 P: 96 healthy adults aged 18–50 years enrolled in a phase 1 trial (12 per low-dose group, 24 per full-dose group, 24 controls) in Belgium
I: Two intramuscular doses (day 1 and day 169) of investigational Vi-CRM197+O:2-CRM197 conjugate vaccine (low-dose or full-dose formulations, with or without aluminium hydroxide)
C: Control vaccines (Vi capsular polysaccharide vaccine for first dose and diphtheria–tetanus–acellular pertussis vaccine for second dose)
O: Safety (solicited and unsolicited adverse events, laboratory abnormalities, serious adverse events); immunogenicity (anti-Vi and anti-O:2 IgG geometric mean concentrations, geometric mean ratios, and seroresponse rates) 		The investigational vaccine was well tolerated, with solicited local and systemic adverse events common but mostly mild and comparable to control, and no serious adverse events reported. Full-dose formulations induced substantially higher anti-Vi IgG responses at day 29 compared with control (GMR 53.01 without aluminium hydroxide and 31.55 with aluminium hydroxide vs 4.50), while full-dose and low-dose formulations without aluminium hydroxide elicited the strongest anti-O:2 IgG responses (GMRs 162.61 and 114.19 vs 1.27). High seroresponse rates were observed after a single dose (89–100% for anti-Vi IgG ≥4.3 μg/mL and 82–100% for ≥4-fold anti-O:2 IgG increase), whereas responses in the control group were markedly lower. A second dose did not meaningfully boost antibody responses. Moderate risk: The observer-masked randomized design reduces detection bias for immunogenicity outcomes, but the single-centre phase 1 setting and small group sizes limit generalizability. Use of sealed-envelope randomisation may introduce selection bias if allocation concealment was imperfect. The study was not powered for comparative efficacy, and short-term follow-up for immunogenicity constrains inference on durability of response.
Salminen P, Salminen R, Kallio J, Hurme S, Nordström P, Rantanen T, et al. Antibiotic therapy for uncomplicated acute appendicitis: ten-year follow-up of the APPAC randomized clinical trial. JAMA. 2026 Jan 21; doi:10.1001/jama.2025.25921 P: 257 adults aged 18–60 years with CT-confirmed uncomplicated acute appendicitis, originally enrolled in the APPAC randomized clinical trial and assigned to antibiotics, with 253 (98.4%) assessed at 10-year follow-up
I: Antibiotic therapy (intravenous ertapenem 1 g/day for 3 days followed by oral levofloxacin 500 mg once daily and metronidazole 500 mg three times daily for 7 days)
C: Appendectomy (open appendectomy; comparator group from original RCT for secondary outcomes)
O: 10-year appendicitis recurrence (histopathologically confirmed); cumulative appendectomy rate; complications; quality of life 		Over 10 years, the true appendicitis recurrence rate among patients initially treated with antibiotics was 37.8% (95% CI 31.6%–44.1%), and the cumulative appendectomy rate was 44.3% (95% CI 38.2%–50.4%). Complications were significantly lower in the antibiotics group compared with the appendectomy group (8.5% vs 27.4%, P<.001). No significant difference in long-term quality of life was observed between treatment strategies (median health index value 1.0 in both groups, P=.18). These findings indicate that although nearly half of patients treated with antibiotics eventually underwent appendectomy, a substantial proportion avoided surgery long term with fewer overall complications. Moderate risk: This analysis represents a long-term observational follow-up of a randomized trial, preserving the strengths of initial randomization but introducing potential attrition and post-randomization bias over 10 years. Near-complete follow-up (98.4%) minimizes attrition bias, and histopathologic confirmation strengthens outcome validity. However, treatment crossover, post hoc analyses, and reliance on secondary and observational endpoints limit causal inference compared with the original RCT design.
Donovan J, Bang ND, Trinh Dong HK, Ho DTN, Nguyen TAT, Nguyen TTH, et al. Genotype-stratified adjunctive dexamethasone for tuberculous meningitis in HIV-negative adults: a randomized controlled phase 3 trial. Nat Med. 2026 Jan 15; doi:10.1038/s41591-025-04138-z P: 702 HIV-negative Vietnamese adults with tuberculous meningitis enrolled in a phase 3 trial, including 613 LTA4H CC- or CT-genotype participants randomized (305 dexamethasone; 308 placebo) and 89 TT-genotype participants treated with open-label dexamethasone
I: Adjunctive dexamethasone for 6–8 weeks in addition to standard antituberculous therapy
C: Placebo (for LTA4H CC- and CT-genotype participants); no randomized comparator for TT-genotype participants
O: Composite of all-cause death or new neurological event within 12 months; serious adverse events 		Among LTA4H CC- and CT-genotype participants, the primary endpoint occurred in 35.4% of patients receiving dexamethasone and 35.7% receiving placebo (HR 0.99, 96% CI 0.75–1.31), demonstrating no superiority of dexamethasone and failing to establish noninferiority of placebo. No heterogeneity of treatment effect was observed across prespecified subgroups or individual genotypes. The number of primary outcome events exceeded the prespecified target, strengthening precision but not altering conclusions. TT-genotype participants receiving open-label dexamethasone had a similar event rate (31.5%) to CC and CT groups, with no significant outcome advantage. Serious adverse events were common but comparable between dexamethasone and placebo in CC/CT participants (52.8% vs 51.9%), indicating acceptable safety without clinical efficacy benefit in these genotypes. Moderate risk: The randomized, placebo-controlled design with adequate event accrual reduces selection and detection bias in CC and CT genotypes. However, exclusion of TT-genotype participants from randomization and their open-label treatment limits genotype-wide causal inference. The composite endpoint may dilute effects on mortality alone, and genotype-stratified analyses reduce power for subgroup conclusions. Overall internal validity is reasonable, but biological stratification and complex design constrain generalizability.
Libby TE, Karani A, Tickell KD, Akech D, Singa B, Rwigi D, et al. The effect of a 5-day course of azithromycin on Streptococcus pneumoniae carriage and antimicrobial resistance among Kenyan children discharged from hospital. J Infect Dis. 2026 Jan 16; doi:10.1093/infdis/jiag028 P: 1,398 hospitalized Kenyan children enrolled in a randomized trial and followed post-discharge (702 azithromycin; 696 placebo), with pneumococcal resistance assessed in a random sample of isolates
I: Oral azithromycin for 5 days administered at hospital discharge
C: Placebo
O: Nasopharyngeal pneumococcal carriage and proportion of isolates resistant to azithromycin at discharge, 3 months, and 6 months 		Pneumococcal carriage did not differ between azithromycin and placebo groups at discharge (22.5% vs 24.6%, P=.40), 3 months (65.6% vs 67.0%; PR 0.98, 95% CI 0.90–1.06), or 6 months (66.7% vs 66.5%; PR 1.00, 95% CI 0.92–1.08). Azithromycin resistance among isolates was similar between groups at 3 months (13.2% vs 12.5%; PR 1.06, 95% CI 0.86–1.66) and 6 months (16.7% vs 17.6%; PR 1.01, 95% CI 0.69–1.49). High background inpatient antibiotic exposure (89.6% of children) likely attenuated any additional effect of post-discharge azithromycin on carriage or resistance. Moderate risk: The double-blind, placebo-controlled randomized design with stratification by site limits selection and performance bias. However, resistance outcomes were assessed only in a random subset of isolates, reducing precision. High baseline and inpatient antibiotic use may have confounded the intervention effect, and findings may not generalize to lower antibiotic-exposure settings.
Gaston DC, Humphries RM, Lewis AA, Gatto CL, Wang L, Nelson GE, et al. Effect of direct-from-blood bacterial testing on antibiotics administration in adults presenting with acute infection: a randomized trial. Clin Infect Dis. 2026 Jan 15; doi:10.1093/cid/ciaf677

• Editorial Commentary:
Coffey KC, Shenoy ES, Turbett SE. The tantalizing pursuit for a perfect diagnostic test: balancing innovation with stewardship. Clin Infect Dis. 2026 Jan 15; doi:10.1093/cid/ciaf674 		P: 500 hospitalized adults with suspected infection receiving empiric intravenous vancomycin in the emergency department of an academic medical center
I: Direct-from-blood bacterial testing in addition to standard blood cultures
C: Standard blood cultures alone (usual care)
O: Time from randomization to last dose of intravenous vancomycin and systemic antipseudomonal beta-lactam antibiotics; clinical outcomes 		Direct-from-blood bacterial testing reduced the time to results by a median of 5.2 days (0.4 vs 5.5 days). However, time to last dose of intravenous vancomycin did not differ significantly between groups (median 12.5 vs 19.0 hours; HR 1.08, 95% CI 0.90–1.28; P=0.42), nor did time to last dose of systemic antipseudomonal beta-lactams (HR 1.04, 95% CI 0.87–1.24). Clinical outcomes were also similar, indicating no meaningful impact of the intervention on antibiotic de-escalation or patient outcomes. Low to moderate risk: Randomized, pragmatic design with well-defined primary and secondary outcomes reduces selection and detection bias. Open-label design could influence clinician behavior but objective timing endpoints limit performance bias. Single-center setting may limit generalizability. No significant missing data reported, minimizing attrition bias.
Miller LG, Kolar S, Sanders J, Williamson J, Allyn PR, Baang J, et al. A phase 2a randomized, double-blind, controlled trial of the efficacy and safety of an intravenous (IV) bacteriophage cocktail (AP-SA02) vs. placebo in combination with best available antibiotic therapy (BAT) in patients with complicated Staphylococcus aureus bacteremia. Open Forum Infect Dis. 2026 Jan 11;13(Suppl 1):ofaf695.022. doi:10.1093/ofid/ofaf695.022 P: 42 adults with complicated Staphylococcus aureus bacteremia (29 AP-SA02; 13 placebo) enrolled across 17 sites (95% US), with MRSA in 39–44% of participants
I: Intravenous bacteriophage cocktail AP-SA02 q6h for 5 days plus best-available therapy (BAT)
C: Placebo plus BAT
O: Clinical response at Test of Cure (Day 12), post-BAT, and End of Study (4 weeks after BAT); safety; secondary outcomes including CRP normalization, time to negative blood culture, ICU/hospital stay 		Clinical response at Day 12 was higher in the AP-SA02 group versus placebo (88% vs 58% by blinded site investigators, p=0.047; 83% vs 58% by independent adjudication). At post-BAT and EOS, non-response/relapse rates were 0% in AP-SA02 versus 23–25% in placebo (p<0.025). Patients receiving AP-SA02 showed trends toward faster CRP normalization, shorter time to negative blood culture, and reduced ICU/hospital stay. Treatment-emergent adverse events were low and comparable (6% AP-SA02 vs 0% placebo). Overall, AP-SA02 demonstrated early and sustained clinical efficacy with a favorable safety profile. Moderate risk: Phase 2a, double-blind, randomized design with blinded adjudication reduces selection and detection bias. Small sample size (42 patients) limits statistical power and precision, particularly for subgroup analyses. Single-country predominance (95% US sites) may affect generalizability. Safety follow-up was limited to 4 weeks post-therapy; longer-term outcomes remain unknown.
Saso A, Fröberg J, Jobe H, Eleveld M, Okoye M, Kanteh E, et al. Mucosal immune responses to Bordetella pertussis in Gambian infants after maternal and primary vaccination: an immunological substudy of a single-centre, randomised, controlled, double-blind, phase 4 trial. Lancet Microbe. 2026 Jan 7;7(1101219): doi:10.1016/j.lanmic.2025.101219 P: 160 infants enrolled in the Gambian Pertussis Study (GaPs), born to healthy mothers aged 18–40 years who received either Tdap–IPV or TT vaccine during pregnancy
I: Infant primary immunisation series with three doses of diphtheria–tetanus–whole-cell pertussis (DTwP) vaccine at 8, 12, and 16 weeks
C: Infant primary immunisation series with three doses of diphtheria–tetanus–acellular pertussis (DTaP) vaccine at the same schedule
O: Nasal mucosal IgG and IgA to B pertussis and pertussis toxin, and nasal T-cell-associated cytokines at 17 weeks and 9 months 		Infants born to Tdap–IPV–vaccinated mothers had higher maternally derived nasal anti-pertussis toxin and anti-B pertussis IgG at 8 weeks pre-vaccination. After primary immunisation, DTwP-vaccinated infants had higher nasal anti-B pertussis IgG and stronger nasal T-cell cytokine responses than DTaP-vaccinated infants, irrespective of maternal vaccine. DTaP-vaccinated infants born to Tdap–IPV–vaccinated mothers showed the lowest mucosal IgG responses, indicating blunting by maternal antibodies. Overall, DTwP induced broader mucosal humoral and cellular immunity, while maternal Tdap–IPV modulated pertussis toxin-specific IgG responses. Moderate risk: Randomised, double-blind design for maternal and infant allocation reduces selection and detection bias. Single-centre immunological substudy and relatively small sample size limit generalizability. Measurement of nasal antibodies and cytokines is objective, but mucosal sampling in infants may be variable. Findings are primarily mechanistic; clinical protection outcomes were not directly measured.
Scott K Heysell, Stellah G Mpagama, Edwin Nuwagira, Bibie Said, Mark Conaway, Megan Null, et al. Immediate or high-dose antituberculosis therapy for HIV-related sepsis in Tanzania and Uganda (ATLAS): a phase 3, open-label, randomised, controlled, 2 × 2 factorial, superiority trial. Lancet Infect Dis. 2026 Jan 28; doi:10.1016/S1473-3099(25)00747-9

• Comment:
Azimia M, Menzies D. Strength of ATLAS or lady luck in a sepsis management trial? Lancet Infect Dis. 2026 Jan 28; doi:10.1016/S1473-3099(26)00025-3 		P: 395 adults living with HIV hospitalised with sepsis in Tanzania and Uganda (57% female, 43% male; all Black; 204 [52%] with microbiologically confirmed TB)
I: Immediate antituberculosis therapy, either conventional-dose (rifampicin 10 mg/kg, isoniazid 5 mg/kg, pyrazinamide, ethambutol) or high-dose (rifampicin 30 mg/kg, isoniazid 7.5 mg/kg, pyrazinamide, ethambutol) daily for 28 days
C: Diagnosis-dependent antituberculosis therapy (started only after clinical or microbiological confirmation), conventional- or high-dose
O: 28-day mortality, adverse events 		Overall 28-day mortality did not differ between immediate versus diagnosis-dependent therapy (25% vs 25%; aHR 0.99, 95% CI 0.67–1.46) or high-dose versus conventional-dose therapy (26% vs 25%; aHR 1.07, 95% CI 0.72–1.59). In patients with confirmed tuberculosis, immediate conventional-dose therapy reduced 28-day mortality compared with diagnosis-dependent conventional-dose therapy (12% vs 34%; aHR 0.32, 95% CI 0.13–0.82; p=0.015). No significant differences in adverse events were observed, though drug-induced liver injury was numerically higher in the immediate high-dose group. Moderate risk: Open-label design could introduce performance or detection bias. Randomisation with allocation concealment and stratification by country/mental status strengthens internal validity. High follow-up completion for primary outcome minimizes attrition bias, but subgroup analyses are limited by smaller numbers, potentially affecting precision of effect estimates. Adherence challenges in critically ill patients may influence intervention effectiveness.

Trial Protocols / Trial Ideas

Prasad N, Nambiar S. Strategic demonstration of the clinical utility of nontraditional antibacterials. Infect Dis Clin North Am. 2025 Dec 18; doi:10.1016/j.idc.2025.11.006

  • Summary: While antimicrobial stewardship (AMS) programs have successfully reduced inappropriate antibiotic use, they have simultaneously limited the market uptake and commercial viability of new antimicrobial agents for resistant infections, highlighting the need to consider regulatory approaches, reimbursement strategies, clinical trial designs, guideline integration, and careful indication selection to support the development and adoption of nontraditional antimicrobial therapies.

Antibiotic Therapy Reviews

Cascio A, Pipitò L, Paterson DL. How to treat carbapenem-resistant Acinetobacter baumannii infections: current knowledge and personal viewpoints. Infect Dis Clin North Am. 2026 Jan 13; doi:10.1016/j.idc.2025.12.001

  • Summary: This article reviews the challenges and current treatment strategies for carbapenem-resistant Acinetobacter baumannii (CRAB), a highly drug-resistant pathogen causing severe infections with high mortality, highlighting sulbactam/durlobactam as first-line therapy, cefiderocol and eravacycline as important options in combination regimens, the selective use of colistin, and emerging novel drugs and approaches, while emphasizing the need to consider infection site, drug pharmacokinetics, combination therapy, and source control for optimal outcomes.

Chang YT, Lu PL, Paterson DL. Current management strategies for Stenotrophomonas maltophilia. Infect Dis Clin North Am. 2025 Dec 13; doi:10.1016/j.idc.2025.11.004

  • Summary: This article reviews current strategies for treating Stenotrophomonas maltophilia, an opportunistic, multidrug-resistant bacterium. Optimal therapy is unclear, but evidence supports combination therapy for immunocompromised or critically ill patients, as no single drug reliably kills the bacteria. Traditional agents like TMP-SMX, levofloxacin, and minocycline remain central, while newer options such as cefiderocol and aztreonam-avibactam are promising but require more clinical validation. Treatment decisions should consider patient severity, immune status, antibiotic susceptibility, and PK/PD data, with future randomized trials needed to define the best regimens.

Di Bella S, Geremia N, Pea F, Zeitlinger M, Sanson G, Monticelli J, et al. When and how to use subcutaneous antibiotics. Clin Infect Dis. 2026 Jan 20; doi:10.1093/cid/ciaf691

  • Summary: This article reviews subcutaneous antibiotic administration as an alternative to intravenous therapy, especially for patients with poor veins, frailty, or in outpatient/palliative settings. It is effective for time-dependent antibiotics like β-lactams and glycopeptides, achieving similar PK/PD targets to IV delivery while reducing catheter complications. Concentration-dependent drugs (e.g., aminoglycosides, fluoroquinolones) show limited benefit, whereas daptomycin performs well. Overall, subcutaneous therapy is well tolerated, though regulatory guidance is limited.

Portales Castillo CA, Hernández Acosta RA, Stewart AG. Severe bacterial infections due to multidrug-resistant organisms in solid organ transplant recipients. Infect Dis Clin North Am. 2026 Jan 2; doi:10.1016/j.idc.2025.12.003

  • Summary: Solid organ transplant recipients are at high risk of colonization and infection with multidrug-resistant organisms, leading to increased morbidity, mortality, and graft complications, and effective management requires understanding epidemiology, risk factors, therapeutic options, and infection control and antibiotic stewardship strategies.

Phage Therapy

Cho E, Kim J, Won T, Ryu S, Jeon B. Virulent bacteriophages for controlling Shiga toxin–producing Escherichia coli without inducing toxin production. J Infect Dis. 2026 Jan 15;233(1):87–95. doi:10.1093/infdis/jiaf035

PK/PD and Drug Dosing

Nielsen MBD, Mikkelsen MKD, Rasmussen HC, Hvistendahl MA, Lützhøft CH, Slater J, et al. Cefepime/enmetazobactam for Gram-negative periprosthetic joint infections? A randomized porcine study on target tissue pharmacokinetics. J Antimicrob Chemother. 2026 Feb;81(2):dkaf487. doi:10.1093/jac/dkaf487

  • Summary: In a preclinical porcine study, cefepime/enmetazobactam achieved high tissue concentrations and met pharmacokinetic/pharmacodynamic targets in bone, synovial fluid, and subcutaneous tissue, suggesting it could be an effective carbapenem-sparing option for Gram-negative periprosthetic joint infections.

Almangour TA, Almosabhi LS, Almojel R, Althubaity R, Almuhisen S, Almohaizeie A, et al. Daptomycin dosing based on adjusted body weight in obese patients versus actual body weight: a multicentre cohort study. Infect Drug Resist. 2026 Jan 13;1–14. doi:10.2147/IDR.S572989

  • Summary: In obese patients, daptomycin dosing based on adjusted body weight showed similar effectiveness and safety compared with dosing based on actual body weight in both obese and non-obese patients, suggesting AdjBW is a viable dosing strategy.

Williamson R, Zurawska M, Valadez A, Harlan E, Scheetz MH, Neely MN, et al. Critical threshold target attainment rates for tazobactam combined with piperacillin among patients admitted to the ICU with hospital-acquired pneumonia. Antimicrob Agents Chemother. 2026;doi:10.1128/aac.01766-25

  • Summary: This study developed a pharmacokinetic model of tazobactam in ICU patients with hospital-acquired pneumonia, showing that standard dosing achieves effective beta-lactamase inhibition for typical targets, but higher targets in patients with high or augmented renal function may require dose adjustments, continuous infusion, or therapeutic drug monitoring.

Antibiotics - In vitro susceptibility

Fan M, Zhang Z, Liu X, Deng L, Lei Y, Chen F, et al. Phylogenetic diversification and fitness trade-offs of TetA variants in mediating eravacycline resistance in Klebsiella pneumoniae. Antimicrob Agents Chemother. 2025 Dec 30;doi:10.1128/aac.00671-25

  • Summary: This study analyzed 28 TetA variants in Klebsiella pneumoniae, finding that a few confer eravacycline resistance but carry significant fitness costs that limit their spread, highlighting evolutionary constraints on antibiotic resistance and the importance of One Health surveillance.

Tascini C, Bianco G, Bonomo RA, Gaibani P. In vitro activity of cefepime/zidebactam against sulbactam/durlobactam-susceptible and -resistant Acinetobacter baumannii clinical isolates. J Antimicrob Chemother. 2026 Feb;81(2):dkaf467. doi:10.1093/jac/dkaf467

  • Summary: This study demonstrated that cefepime combined with the β-lactam enhancer zidebactam exhibited potent in vitro bactericidal activity against carbapenem-resistant Acinetobacter baumannii (CRAB) strains regardless of their susceptibility to sulbactam/durlobactam, while cefepime/enmetazobactam showed no activity, highlighting cefepime/zidebactam as a promising therapeutic option for OXA-producing CRAB isolates.

Bianco G, Biffignandi GB, Boattini M, Comini S, Costa C, Vumbaca M, et al. Resistance to sulbactam/durlobactam in carbapenem-resistant Acinetobacter baumannii in treatment-naive setting: in vitro data and genomic insights from Italian bloodstream isolates. Int J Antimicrob Agents. 2026 Jan 16;107718. doi:10.1016/j.ijantimicag.2026.107718

  • Summary: Analysis of 110 CRAB bloodstream isolates from Italy revealed that sulbactam/durlobactam inhibited 88.7% of strains, while resistance was linked to blaOXA-23 and blaNDM-1 carbapenemases, mutations in penicillin-binding proteins, and clonal outbreaks of ST231 and ST837/ST369 lineages, underscoring the need for ongoing genomic surveillance and prudent antibiotic stewardship to control resistant A. baumannii dissemination.

Mezcord V, Luu I, Akhar U, Traglia GM, Rodríguez C, Moheb S, et al. Vitamin B12 promotes cefiderocol resistance and small-colony variants in carbapenem-resistant Acinetobacter baumannii. mBio. 2026 Jan 16;doi:10.1128/mbio.03760-25

  • Summary: Vitamin B12 supplementation was shown to increase cefiderocol minimum inhibitory concentrations and promote persistent small-colony variants in carbapenem-resistant Acinetobacter baumannii by competitively interacting with TonB-dependent receptors and altering gene expression, revealing a novel host–pathogen–drug interaction that may contribute to treatment failure and suggesting the need to consider micronutrient effects in antimicrobial therapy.

Dutkiewicz M, Jousset AB, de Swardt H, Rezzoug I, Bonnin RA, Dortet L, Emeraud C. In vitro susceptibility of cefepime-enmetazobactam, cefepime-taniborbactam and cefepime-zidebactam towards carbapenemase-producing Enterobacterales. J Antimicrob Chemother. 2026 Jan;81(1):dkaf440. doi:10.1093/jac/dkaf440

  • Summary: Evaluation of three novel β-lactam/β-lactamase inhibitor combinations against 1600 carbapenemase-producing Enterobacterales isolates showed that cefepime-zidebactam exhibited the broadest activity across KPC, OXA-48-like, VIM, and NDM producers, cefepime-taniborbactam was highly effective against KPC, OXA-48-like, and VIM but less so for NDM, and cefepime-enmetazobactam was selectively active, indicating these combinations could serve as targeted therapies depending on specific resistance profiles.

Zocche G, Lewis RE, Bianco G, Tascini C, Gaibani P. In vitro interactions of sulbactam/durlobactam in combination with meropenem, ceftazidime/avibactam, piperacillin/tazobactam, cefiderocol and fosfomycin against carbapenem-resistant Acinetobacter baumannii (CRAB) clinical isolates. Eur J Clin Microbiol Infect Dis. 2026 Jan 8;doi:10.1007/s10096-025-05398-w

  • Summary: Sulbactam/durlobactam in combination with piperacillin/tazobactam or ceftazidime/avibactam demonstrated synergistic activity against 53.8% of carbapenem-resistant Acinetobacter baumannii clinical isolates, including strains resistant to sulbactam/durlobactam alone, and restored meropenem susceptibility in nearly half of tested strains, highlighting combination therapy as a potential strategy for overcoming CRAB resistance.

Beta-Lactamases and Other Resistance Mechanisms

Boattini M, Comini S, Ricciardelli G, Pastrone L, Casale R, Guarrasi L, et al. Emergence of resistance to novel β-lactam/β-lactamase inhibitor combinations in KPC-producing Klebsiella pneumoniae: clinical and genomic insights from consecutive bloodstream infections. Infection. 2025 Dec 23;doi:10.1007/s15010-025-02716-4

  • Summary: This study of 178 KPC-producing Klebsiella pneumoniae bloodstream isolates in an Italian hospital found that while aztreonam/avibactam, meropenem/vaborbactam, and imipenem/relebactam remained highly effective (≥96% susceptible), resistance to ceftazidime/avibactam affected 11% of isolates, driven by diverse KPC variants and porin disruptions, often emerging after prior colonization and recent β-lactam exposure, with 28-day mortality of 21.7%, highlighting the need for continuous genomic surveillance and stringent antimicrobial stewardship to sustain the efficacy of these last-line β-lactam/β-lactamase inhibitor combinations.

Adverse effects from antimicrobial agents

Zhao YL, Qu Q, Wang YM, Zhang YT, Qu J. A disproportionality analysis of adverse events associated with omadacycline based on the FDA adverse event reporting system database. J Antimicrob Chemother. 2026 Feb;81(2):dkag006. doi:10.1093/jac/dkag006

  • Summary: Analysis of 4541 post-marketing reports from the FDA Adverse Event Reporting System revealed that omadacycline, a novel aminomethylcycline for community-acquired infections, is primarily associated with gastrointestinal adverse effects such as nausea, vomiting, and diarrhea, along with notable safety signals including tooth and tongue discoloration, Mycobacterium avium complex infection, hepatic events, and 49 reported deaths, indicating the need for careful monitoring of elderly and comorbid patients and ongoing pharmacovigilance to ensure safe use in real-world settings.

Antibiotic Stewardship and Hospital in the Home

Umer M, Jagra AS, Hanif FM, Khan M, Sharma H. Seven days versus extended duration antibiotic therapy for multidrug-resistant gram-negative bacterial infections in critically ill patients: a pooled analysis of the OPTIMISE and REGARD-VAP trials. J Crit Care. 2026 Apr;92:155361. doi:10.1016/j.jcrc.2025.155361

  • Summary: A meta-analysis pooling data from the OPTIMISE and REGARD-VAP trials in 602 ICU patients with multidrug-resistant Gram-negative bacterial infections found that short-course antibiotic therapy (6–9 days) was comparable to extended therapy (7–14 days) in terms of mortality and clinical failure, with a non-significant trend toward higher relapse, suggesting that shorter regimens may be effective but warrant further investigation for pathogen- and patient-specific factors.

Albers B, Nagavci B, Joean O, Tschudin Sutter S, Tacconelli E, Paul M, et al. Guiding principles for implementing ESCMID clinical practice guidelines. Clin Microbiol Infect. 2026 Jan 27;doi:10.1016/j.cmi.2026.01.012

  • Summary: This guide outlines best practices for implementing clinical practice guidelines (CPGs), using the ESCMID infection guidelines as an example, emphasizing that effective uptake requires understanding the local healthcare context, tailoring guideline application to that context, and rigorously monitoring implementation outcomes through frameworks like RE-AIM/PRISM to enhance applicability, sustainability, and impact on patient care.

Berry R, Catteau L, Caris MG, de Boer MGJ, Kherabi Y, Magrini E, et al. Identifying indicators for measuring appropriateness of antibiotic prescribing in high-income countries: a rapid systematic review. Clin Microbiol Infect. 2026 Jan 26;doi:10.1016/j.cmi.2026.01.011

  • Summary: A rapid systematic review of 165 studies across high-income countries identified 103 indicators for measuring the appropriateness of antibiotic prescribing, including patient-specific and proxy measures such as guideline compliance, correct antibiotic choice, dose, and duration, revealing inappropriate prescribing rates from 2% to 88% and providing a comprehensive resource to guide antimicrobial stewardship efforts.

Chamawan P, Limmathurotsakul D. How to utilize routine antimicrobial resistance surveillance data for local and national actions in an LMIC. JAC Antimicrob Resist. 2025 Dec;7(6):dlaf225. doi:10.1093/jacamr/dlaf225

  • Summary: In Thailand, over 100 hospitals were supported to use antimicrobial resistance (AMR) surveillance data effectively for local infection control and national policy-making, with guidance including data validation, trend comparisons, benchmarking, cluster analysis, and development of empirical therapy guidelines, offering a framework that other low- and middle-income countries can adapt to optimize AMR-informed actions.

Goto M, Bandyopadhyay A, Shi Q, Wang Y, Perencevich EN, Hernandez D, et al. Personalized antibiogram: a novel multi-task machine learning framework for simultaneous prediction of antimicrobial resistance profile with enhanced detection of carbapenem resistance in Enterobacteriaceae. Clin Infect Dis. 2026 Jan 17;ciag027. doi:10.1093/cid/ciag027

  • Summary: A multi-task XGBoost machine learning model was developed using EHR data from 127 Veterans Health Administration sites to simultaneously predict resistance profiles for eight antimicrobial classes in E. coli and Klebsiella spp., achieving AUROCs of 0.779–0.810, improving calibration, reducing false negatives for carbapenem resistance, and enabling personalized antibiograms that outperform conventional antibiograms and single-target models for empiric therapy guidance.

Infection Prevention / Antibiotic Prophylaxis

Merrick B, Cooper R, Davido B, Goldenberg S. The role of the gut microbiome in MDRO colonisation and infection. Clin Microbiol Infect. 2026 Jan 22;doi:10.1016/j.cmi.2026.01.009

  • Summary: A comprehensive review of evidence on the gut microbiome highlights its critical role in providing colonisation resistance against multidrug-resistant organisms (MDROs), showing that antibiotics, diet, travel, and healthcare exposures can disrupt microbiota and increase MDRO acquisition risk, and emphasizing that interventions such as microbiome-sparing antimicrobial regimens, probiotics, dietary strategies, and fecal microbiota transplantation should be rigorously evaluated and integrated into clinical and public health policies to reduce MDRO burden.

Tiseo G, Galfo V, Lepore A, Pogliaghi M, Suardi LR, Giordano C, et al. Risk factors for bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii in ICU patients with any site colonization: a prospective observational study. Int J Antimicrob Agents. 2026 Jan 12;107717. doi:10.1016/j.ijantimicag.2026.107717

  • Summary: A prospective observational study of 283 ICU patients colonized with carbapenem-resistant Acinetobacter baumannii (CRAB) developed a risk score for predicting bloodstream infections, identifying burns, multisite colonization, respiratory tract colonization, and cardiovascular disease as key predictors, with the resulting model achieving an AUC of 0.817 and a high negative predictive value, suggesting it could guide rational empirical antibiotic use after external validation.

Saad BAA, Volpe-Chaves CE, Flores de Oliveira CT, Stavis Conte B, Lacerda MLGG, Venturini J, et al. The emerging clinical relevance and antimicrobial resistance of Pluralibacter gergoviae: a systematic review. J Antimicrob Chemother. 2026 Feb;81(2):dkaf476. doi:10.1093/jac/dkaf476

  • Summary: A systematic review of 34 studies describing 196 patients infected with Pluralibacter gergoviae revealed that infections are rare but predominantly healthcare-associated, often occurring in ICUs including neonatal units, with 33% of strains multidrug-resistant and carbapenemase genes blaKPC, blaNDM, and blaIMP present; prior antibiotic use was associated with mortality, underscoring the pathogen’s clinical relevance and risk in vulnerable populations.

Doll CL, Opalka R, Nguifo LT, Talom AT, Kuate Kamdem L, Will A, et al. How to get cheap clean air? Implementation of an affordable high-efficient air filtration ventilation system for operating theatres in a low-resource setting. GMS Hyg Infect Control. 2026;21:Doc06. doi:10.3205/dgkh000615

  • Summary: A locally constructed, affordable (3,500 €) mechanical air filtration system for operating theatres in a district hospital in Cameroon demonstrated >97% particle reduction and 72% reduction in microbial contamination after four years of use, providing a feasible, context-adapted alternative to expensive standard air filtration systems and improving air cleanliness compared to natural ventilation, although full DIN/ISO compliance was not achieved.

Gastrointestinal Tract Infections

Baumgart SWL, Watt A, Sullivan G, Drew A, Suliman B, Wang Q, et al. Carbapenemase-producing non-typhoidal salmonellae: do we need to standardise algorithms for susceptibility testing in routine practice? Pathology. 2026 Feb;58(1):103–5. doi:10.1016/j.pathol.2025.07.006

  • Summary: A case report from Australia described an extensively drug-resistant (XDR) Salmonella enterica serovar Rissen (ST469) isolated from an immunocompetent 51-year-old woman with gastrointestinal symptoms but no prior antibiotic exposure; phenotypic and whole-genome sequencing confirmed carbapenemase production and multiple antimicrobial resistance genes, highlighting concerns for surveillance, susceptibility testing, and monitoring of XDR non-typhoidal Salmonella.

Wang Y, Shao H, Jin Z, Zhu H, Chang Z, Teng G. Liver abscess formation after transarterial chemoembolization in patients with hepatocellular carcinoma: a multicenter retrospective study (CHANCE 2407). Clin Microbiol Infect. 2026 Jan 27;doi:10.1016/j.cmi.2026.01.016

  • Summary: A nested case-control study investigated risk factors for liver abscess formation following transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma, aiming to identify subgroups who might benefit from prophylactic antibiotics to reduce abscess incidence while avoiding unnecessary use in all patients.

Guo JY, Lin WS, Lin CH, Wu MC. Appendectomy and risk of nonyphoidal Salmonella infection in children. JAMA Netw Open. 2026 Jan 23;9(1):e2555278. doi:10.1001/jamanetworkopen.2025.55278

  • Summary: A nationwide population-based cohort study in Taiwan found that children who underwent appendectomy had a 1.58-fold higher risk of subsequent non-typhoidal Salmonella (NTS) infection compared with matched controls, particularly in children under 5 years old, suggesting the appendix may play a protective role in gut immunity and that post-appendectomy surveillance and preventive strategies may be warranted.

Bone and Joint Infections

Jordan V, Davis JS, Naqvi S. Assessing yield and impact of 5-day versus 10-day incubation time in suspected prosthetic joint infection: a prospective laboratory study. Pathology. 2026 Feb;58(1):85–8. doi:10.1016/j.pathol.2025.07.004

  • Summary: A prospective study of 280 prosthetic joint samples from 53 patients evaluated whether extending incubation from 5–7 to 10 days improved detection of clinically relevant bacteria in suspected prosthetic joint infections (PJI); only 2% of samples yielded additional potentially significant pathogens, while 70% of non-significant growth occurred during extended incubation, suggesting that routine prolonged incubation increases contamination risk without clear clinical benefit.

CNS Infections

Lazarus G, Caddey B, Dean A, Febrina F, Wangsaputra VK, Radiani SP, et al. Antimicrobial resistance in bacterial meningitis caused by Streptococcus pneumoniae, Neisseria meningitidis, or Haemophilus influenzae (2010–24): a systematic review and meta-analysis. Lancet Microbe. 2026 Jan 27;doi:10.1016/j.lanmic.2025.101238

  • Summary: A systematic review and meta-analysis of 16,441 meningitis isolates from 37 countries found high and regionally variable antimicrobial resistance among Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae, with rising penicillin resistance in low- and middle-income countries, highlighting the urgent need to strengthen national antimicrobial resistance surveillance to guide treatment and public health interventions.

Chavanet P, Matheux A, Sixt T, Barbet J, Nau R, Guerard P, et al. Penetration of daptomycin in cerebrospinal fluid during pneumococcal meningitis. J Antimicrob Chemother. 2026 Feb;81(2):dkaf474. doi:10.1093/jac/dkaf474

  • Summary: In 13 patients with pneumococcal meningitis, intravenous daptomycin at 10 mg/kg/day achieved cerebrospinal fluid concentrations exceeding the MIC90 of resistant strains, with CSF penetration correlating with protein and lactate levels, suggesting daptomycin may serve as a non-lytic adjunctive therapy for highly resistant pneumococcal infections.

Yakubovsky M, Kadar L, Katchman E, Regev A, Atamna A, Yelin D, et al. Cat scratch disease encephalitis: new insights into rate, clinical features, and long-term outcomes. Int J Infect Dis. 2026 Jan 14;108395. doi:10.1016/j.ijid.2026.108395

  • Summary: Analysis of a national cat scratch disease registry identified 19 cases (0.5%) of encephalitis/meningoencephalitis, revealing acute and subacute clinical patterns, generally favorable outcomes after long-term follow-up, but persistent cognitive complaints in 42% of patients, indicating the need for further study on treatment strategies including antibiotics and corticosteroids.

Ergönül Ö, Kolsuz S, Figueroa JP. Tetanus. Lancet. 2026 Jan 13;doi:10.1016/S0140-6736(25)01579-X

  • Summary: Despite global vaccination reducing mortality, tetanus still causes 30,000–50,000 deaths annually, particularly among adults with comorbidities; clinical diagnosis and management rely on wound care, antibiotics, and antitoxin, while early autonomic instability and intensive care complications underscore the ongoing need for vaccination, surveillance, equitable access, and novel therapeutic approaches.

Respiratory Tract Infections

Soumare A, Kapfer T, Botrel T, Adda L, Renaux M, Blot PL, et al. Systemic corticosteroids, mortality, and infections in pneumonia and acute respiratory distress syndrome: a systematic review and meta-analysis. Ann Intern Med. 2026 Jan;179(1). doi:10.7326/ANNALS-25-03055

  • Summary: A systematic review and meta-analysis of 20 randomized trials involving 3459 adults with severe non–COVID-19 pneumonia or ARDS found that low-dose, short-course systemic corticosteroids initiated early probably reduce short-term mortality and may reduce secondary shock in severe pneumonia, while having little or no effect on hospital-acquired or secondary infections.

Pieruzzi M, Matucci T, Raccagni AR, Antinori S, Riccardi N, Nozza S, et al. How we treat Nocardia infections in transplant recipients and people with HIV. Clin Microbiol Infect. 2026 Jan 27;doi:10.1016/j.cmi.2026.01.013

  • Summary: This narrative review highlights that nocardiosis is a rare but serious opportunistic infection in solid organ and stem cell transplant recipients and people with advanced HIV, with diagnosis hindered by non-specific presentations and prolonged culture requirements, and management complicated by variable antimicrobial susceptibility and limited evidence-based guidance.

Dequin PF, Torres A, Bassetti M, Ferrer M, Giamarellos-Bourboulis EJ, Martin-Loeches I, et al. Severe community-acquired pneumonia: current concepts and controversies. Intensive Care Med. 2026 Jan;52:118–130. doi:10.1007/s00134-025-08252-x

  • Summary: This review of severe community-acquired pneumonia emphasizes ongoing challenges from resistant pathogens, uncertainty around the role of rapid molecular diagnostics and biomarkers, and conflicting evidence on corticosteroid use, underscoring the need for better patient phenotyping, cautious immunomodulatory therapy, and optimized supportive care.

Dequin PF, Confalonieri M. Glucocorticoid treatment in community-acquired pneumonia. Semin Respir Crit Care Med. 2025 Oct 14;doi:10.1055/a-2704-6851

  • Summary: Despite numerous heterogeneous trials, the role of corticosteroids as adjunctive therapy in community-acquired pneumonia remains controversial, with recent ICU-based studies suggesting potential benefit in selected patients, while reinforcing that corticosteroids are not recommended for influenza and appear generally safe only for short-term use in carefully chosen populations.

Narvaez-Ramirez PO, Bustos IG, Serrano-Mayorga CC, Reyes LF. Pneumonia after solid organ transplantation. Semin Respir Crit Care Med. 2025;doi:10.1055/a-2708-4873

  • Summary: This comprehensive review outlines pneumonia as a leading cause of morbidity and mortality in solid organ transplant recipients, detailing evolving epidemiology, microbial causes, and risk factors, and highlighting the lack of transplant-specific guidelines, the importance of early empirical therapy, and the need for individualized antimicrobial stewardship amid rising resistance.

Smith SAM, Rockett RJ, Oftadeh S, Sintchenko V. Genomic features of Streptococcus pneumoniae associated with recurrent invasive pneumococcal disease. Pathology. 2026 Feb;58(1):89–96. doi:10.1016/j.pathol.2025.08.012

  • Summary: Genomic analysis of 140 Streptococcus pneumoniae isolates from 67 patients with recurrent invasive pneumococcal disease showed that nearly half of recurrences were due to relapse with genetically related strains rather than reinfection, particularly within one year, supporting the use of whole-genome sequencing to guide clinical management and public health follow-up.

Farfour E, Brisebarre A, Corvec S, Guillard T. Current knowledge and perspectives on the emerging Inquilinus limosus pathogen. Clin Microbiol Rev. 2026 Jan 7;doi:10.1128/cmr.00100-25

  • Summary: This review describes Inquilinus limosus as an emerging nonfermentative Gram-negative pathogen predominantly affecting cystic fibrosis patients, summarizing reported clinical cases, identification challenges, phenotypic characteristics, and antimicrobial susceptibilities, while emphasizing the need for complete genome sequencing to better understand its resistance mechanisms and pathogenicity.

Endocarditis

Moffa L, Tana C, Meschi T, Siniscalchi C, Cerundolo N, Ucciferri C, et al. Gut–heart axis and infective endocarditis: how microbiota dysbiosis shapes cardiovascular risk and infection susceptibility. J Clin Med. 2026 Jan 12;15(2):597. doi:10.3390/jcm15020597

Summary: This narrative review explores the gut–heart axis, highlighting how intestinal dysbiosis, impaired gut barrier integrity, immune activation, and microbiota-derived metabolites contribute to cardiovascular diseases, with a particular focus on infective endocarditis arising from gut bacterial translocation, and discusses emerging preventive and therapeutic strategies including microbiota modulation and personalized medicine.

Mycobacterial Infections

Loveday M, Clarence E, Hlangu S, Singh N, Chotoo S, Brust JCM, et al. Pregnant women with MDR/RR-TB and the all-oral 6-month regimen: experiences from a patient series in South Africa. Clin Infect Dis. 2026 Jan 22;ciag032. doi:10.1093/cid/ciag032

  • Summary: In a prospective cohort of pregnant women with MDR/RR-TB in South Africa, all-oral 6-month regimens containing bedaquiline, delamanid, linezolid, and levofloxacin or clofazimine were associated with high maternal treatment success and mostly favourable pregnancy outcomes, but a concerning proportion of infants experienced unfavourable outcomes, underscoring the need for longer-term safety data.

Sweetser B, Nguyen H, Dang H, Katumba D, Mochizuki T, Wang Q, et al. Evaluating the Cepheid Xpert TB/LTBI research-use-only assay for detection of active and latent Mycobacterium tuberculosis infection. Clin Infect Dis. 2026 Jan 21;ciag005. doi:10.1093/cid/ciag005

  • Summary: This multicountry diagnostic study found that the blood-based Xpert TB/LTBI assay demonstrated high accuracy and sensitivity for detecting active tuberculosis and met WHO targets for a TB screening test, although its ability to reliably distinguish active TB from latent infection requires further refinement.

Turner CT, Tiffeau-Mayer A, Rosenheim J, Chandran A, Saxena R, Zhang P, et al. Evolution of the tuberculin skin test reveals generalisable Mtb-reactive T cell metaclones. Nat Commun. 2026 Jan 21;doi:10.1038/s41467-026-68678-9

  • Summary: This study used T cell receptor sequencing at the tuberculin skin test site to track Mycobacterium tuberculosis–reactive T cell clones over time, revealing oligoclonal expansion and identifying a small set of public, immunodominant T cell metaclones that can robustly detect Mtb-specific immunity across populations and may inform patient stratification and vaccine development.

van Lieshout Titan A, Dodd PJ, Cohen T, Menzies NA. Estimating the number of incorrect tuberculosis diagnoses in low- and middle-income countries. Nat Med. 2026 Jan 7;doi:10.1038/s41591-025-04097-5

  • Summary: An analysis of World Health Organization tuberculosis notification data from 111 low- and middle-income countries estimated that in 2023 up to three in ten TB diagnoses were incorrect, with substantial false-positive and false-negative rates, indicating that major improvements in TB control will require more sensitive bacteriological diagnostics and reduced reliance on clinical diagnosis alone.

Pereira CN, Câmara RSB, Lage DP, Corrêa LVA, Freitas CS, Silva AL, et al. Diagnostic evaluation of a novel recombinant multi-epitope protein for paucibacillary and multibacillary leprosy. Tuberculosis. 2026 Mar;157:102732. doi:10.1016/j.tube.2026.102732

  • Summary: This study developed and evaluated a novel recombinant multi-epitope protein (M3) for leprosy diagnosis, demonstrating very high sensitivity and specificity in both serum- and urine-based ELISA for paucibacillary and multibacillary disease, with antibody levels declining after treatment, supporting its potential as a non-invasive diagnostic and treatment-monitoring tool.

Seshadri C, Flynn JAL, Maiello P, Schnappinger D, Wilkinson RJ, Gordon SB, et al. Controlled human infection with Mycobacterium tuberculosis: practical considerations for clinical trials. Lancet Microbe. 2026 Jan 23;doi:10.1016/j.lanmic.2025.101278

  • Summary: This Personal View discusses how recent advances in bacterial engineering may enable ethically acceptable controlled human infection models for pulmonary Mycobacterium tuberculosis, outlining key ethical, safety, and methodological considerations and proposing priority clinical, microbiological, immunological, and imaging endpoints to accelerate TB vaccine development.

Mesfin E, Blumberg HM. Nosocomial TB: the blind spot in global tuberculosis prevention and care. Clin Microbiol Infect. 2026 Jan 19;doi:10.1016/j.cmi.2026.01.008

  • Summary: This article highlights the re-emergence of tuberculosis as the leading global infectious killer in 2023 and emphasizes that nosocomial transmission, including multidrug- and extensively drug-resistant TB, remains underrecognized in high-burden healthcare settings due to diagnostic, surveillance, and resource limitations.

Starke S, Thomas K, Jasuja S, Lubelchek R. Short-course tuberculosis preventive therapy in a high migration setting: early experience with 1HP in Cook County, Illinois. Clin Infect Dis. 2026 Jan 21;ciaf723. doi:10.1093/cid/ciaf723

  • Summary: In a U.S. public health TB program focused on non–U.S.-born populations, most individuals evaluated for latent TB infection initiated and completed preventive therapy, with lower completion among newly arrived migrants, and the one-month isoniazid–rifapentine regimen showing good tolerability and comparable completion to longer regimens.

Ji J, Jiang X, Liao X, Du F, Wang G, Huang H, et al. A monovalent SMAC mimetic as a potential host-directed therapy for tuberculosis. J Infect Dis. 2026 Jan 20;jiag031. doi:10.1093/infdis/jiag031

  • Summary: This study shows that the SMAC mimetic BI82 acts as a host-directed therapy by inducing apoptosis in infected cells, synergizing with rifampicin and reducing mycobacterial burden in vitro, ex vivo, and in mouse models, supporting its potential as a novel anti-tuberculosis strategy.

Otieno JA, Were LM, Lutje V, Scandrett K, Takwoingi Y, Ochodo EA. Impact of rapid nucleic acid amplification tests for tuberculosis on patient outcomes. Cochrane Database Syst Rev. 2025 Dec 18;CD016194. doi:10.1002/14651858.CD016194

  • Summary: This Cochrane review found that use of Xpert MTB/RIF Ultra compared with smear microscopy shortens time to tuberculosis diagnosis and treatment but makes little to no difference in mortality, with limited evidence on cure rates and other patient outcomes.

Youssef A, Salimi S, Cooper W, Horgan L, Liu K. Mycobacterium genavense duodenitis with iron deficiency anaemia in new diagnosis of acquired immunodeficiency syndrome. Pathology. 2026 Feb;58(1):107–9. doi:10.1016/j.pathol.2025.07.005

  • Summary: This case report describes an unusual presentation of Mycobacterium genavense duodenitis causing iron deficiency anaemia in a patient with newly diagnosed AIDS, highlighting diagnostic challenges and the importance of biopsy and clinical suspicion.

Gopalaswamy R, Subbian S. The power of resistance: mechanisms of antimicrobial resistance in Mycobacterium tuberculosis and its impact on tuberculosis management. Clin Microbiol Rev. 2026 Jan 7;doi:10.1128/cmr.00194-25

  • Summary: This review synthesizes molecular, immunological, and pharmacological mechanisms underlying drug-resistant tuberculosis and proposes a precision-based management approach integrating advanced diagnostics, therapeutic drug monitoring, and host-directed therapies.

Nalugwa T, Shah KM, Marcelo D, Nakawunde R, Trinh T, Emmanuel J, et al. Predicted preferences for tuberculosis point-of-care tests among tuberculosis-affected individuals in five high burden countries. Clin Infect Dis. 2026 Jan 14;ciag022. doi:10.1093/cid/ciag022

  • Summary: This discrete choice experiment across five countries shows that people affected by tuberculosis strongly prefer point-of-care diagnostic tests, even when these have slightly lower accuracy than standard facility-based testing.

Niward K, Braian C, Svärdhagen G, Augustinsson D, Öhrnberg I, Ruslami R, et al. Future prospects for using clinical phenotypes in tuberculosis precision medicine—an approach for clinical management. Clin Infect Dis. 2026 Jan 15;ciaf663. doi:10.1093/cid/ciaf663

  • Summary: This article argues that shortening tuberculosis treatment requires precise clinical phenotyping and integrated monitoring using omics, AI-driven algorithms, bacterial load measures, and radiological and symptom scores to enable stratified therapy and relapse-free cure.

Honda JR, Wilsey RN, Raulerson CK, Ding L-H, Castaneda CL, Joyner JL. Documenting environmentally acquired Mycobacterium intracellulare subsp. chimaera pulmonary disease soon after bronchiectasis onset. Clin Infect Dis. 2026 Jan 10;ciag015. doi:10.1093/cid/ciag015

  • Summary: This study links the development of nontuberculous mycobacterial pulmonary disease in a patient with bronchiectasis to long-term household environmental exposure in an NTM hotspot using longitudinal sampling.

Jovanovic A, Bright FK, Sadeghi A, Wicki B, Caño Muñiz SE, Giannini GC, et al. Large-scale testing of antimicrobial lethality at single-cell resolution predicts mycobacterial infection outcomes. Nat Microbiol. 2026 Jan 9. doi:10.1038/s41564-025-02217-y

  • Summary: This study introduces antimicrobial single-cell testing, showing that drug-specific killing dynamics and bacterial tolerance at the single-cell level better predict treatment efficacy and patient outcomes than traditional growth inhibition assays.

Fungal Infections and antifungal agents

Rhodes J, Hui ST, Dellière S, Summerbell RC, Scott JA, Kaur A, et al. Emerging terbinafine-resistant Trichophyton indotineae between 2018 and 2023: a multinational genomic epidemiology study. Lancet Microbe. 2026 Jan 22. doi:10.1016/j.lanmic.2025.101273

  • Summary: This genomic epidemiology study shows that terbinafine-resistant Trichophyton indotineae has a single evolutionary origin, has spread rapidly across continents, and commonly carries SQLE mutations associated with resistance, underscoring the need for enhanced genomic surveillance.

Prattes J, Dichtl K, Sedik S, Glatz U, Egger M, Wölfler A, et al. Diagnostic accuracy of Mucorales PCR testing in bronchoalveolar lavage fluid samples: a retrospective analysis of a prospectively collected cohort. Clin Microbiol Infect. 2026 Jan 27. doi:10.1016/j.cmi.2026.01.017

  • Summary: This diagnostic accuracy study demonstrates that the MucorGenius PCR assay has near-perfect specificity and high sensitivity in bronchoalveolar lavage fluid, supporting its value for diagnosing pulmonary mucormycosis and detecting mixed mold infections.

Clark D, Barranco-Trabi J, Goo I, Chyz M, Manchala G, Davar K, et al. Single-dose liposomal amphotericin plus fluconazole and flucytosine for cryptococcal meningitis at a US public hospital. JAMA Netw Open. 2026 Jan 21;9(1):e2553552. doi:10.1001/jamanetworkopen.2025.53552

  • Summary: This pre-post cohort study found that the AMBITION protocol for HIV-associated cryptococcal meningitis resulted in fewer severe adverse events and improved composite outcomes compared with daily amphotericin regimens, without increasing mortality or recurrence.

Bahr NC, Rajasingham R, Boulware DR. Is it time to use single-dose amphotericin B for HIV-related cryptococcal meningitis? JAMA Netw Open. 2026 Jan 21;9(1):e2553489. doi:10.1001/jamanetworkopen.2025.53489

  • Summary: This commentary argues that real-world US data now strongly support adoption of the single-dose liposomal amphotericin AMBITION regimen, highlighting benefits in safety, patient-centered care, shorter hospitalization, and health-system efficiency.

Candelo E, Vasudevan SS, Osuoha GC, Elijah I, Alhalabi A, Ward BA, et al. Proportion, morbidity, and mortality of acute invasive fungal rhinosinusitis in immunocompromised populations: a systematic review and meta-analysis. JAMA Otolaryngol Head Neck Surg. 2026 Jan 22. doi:10.1001/jamaoto.2025.5077

  • Summary: This systematic review and meta-analysis shows that while the proportion of acute invasive fungal rhinosinusitis among immunocompromised patients has increased over time, mortality has declined, likely due to advances in diagnosis and treatment.

Bartalucci C, Mezzogori L, Schiavoni R, Vena A, Giacobbe DR, Bassetti M. Antifungal treatment strategies in intensive care unit patients. Eur J Clin Invest. 2026 Jan 22. doi:10.1111/eci.70177

  • Summary: This review highlights the challenges of diagnosing invasive candidiasis, invasive pulmonary aspergillosis, and Pneumocystis jirovecii pneumonia in critically ill ICU patients, and emphasizes individualized antifungal therapy, PK/PD-guided dosing, and emerging antifungal agents as key strategies to balance early treatment with antifungal stewardship.

Sivasubramanian G. Valley fever in central California: diagnosis is not the finish line, the real gap is longitudinal care. Clin Infect Dis. 2026 Jan 22;ciaf728. doi:10.1093/cid/ciaf728

  • Summary: This perspective argues that improving outcomes for coccidioidomycosis in California’s San Joaquin Valley requires strengthening continuity of care through community-based, culturally grounded approaches, rather than focusing solely on diagnostic capacity.

Neoh CF, Chen SC-A, Morris AJ, Heath CH, Tan SJ, Lane R, et al. Current epidemiology and infection characteristics of non-Aspergillus mold infections: a multicenter study in Australia and New Zealand. Clin Infect Dis. 2026 Jan 21;ciag029. doi:10.1093/cid/ciag029

  • Summary: This large Australasian multicenter study shows that non-Aspergillus mold infections are most commonly caused by Lomentospora prolificans, Scedosporium species, and Mucorales, often affect patients with hematological malignancy or diabetes, and are associated with high mortality, particularly for L. prolificans and Mucorales.

Reizine F, Mauget M, Massart N, Fedun Y, Machut A, Vacheron C-H, et al. Clinical spectrum of ICU-acquired invasive pulmonary aspergillosis according to SARS-CoV-2 infection: a multicenter prospective cohort study. Eur J Clin Microbiol Infect Dis. 2026 Jan 12. doi:10.1007/s10096-025-05391-3

  • Summary: This multicenter ICU cohort study found that although COVID-19–associated pulmonary aspergillosis occurred more frequently and led to longer ventilation and ICU stays, overall survival was similar to non-COVID invasive pulmonary aspergillosis after adjustment for confounders.

Benedict K, Thompson GR III, Ampel NM, Smith DJ, Toda M, Hennessee I. Blastomycosis, histoplasmosis, and coccidioidomycosis in outpatient community-acquired pneumonia. JAMA Netw Open. 2026 Jan 14;9(1):e2553965. doi:10.1001/jamanetworkopen.2025.53965

  • Summary: This US claims-based cohort study shows that fungal testing for blastomycosis, coccidioidomycosis, and histoplasmosis among outpatients with community-acquired pneumonia is infrequent, often delayed, and associated with specific clinical features, suggesting missed diagnostic opportunities and unnecessary antibiotic use.

Virulence

Zhou Q-Q, Wan Y. Mechanisms of microbial colonization in biofilm-associated infections of hemodialysis catheters and advances in surface modification technologies. Clin Microbiol Rev. 2026 Jan 23. doi:10.1128/cmr.00283-25

  • Summary: This review highlights how microbial colonization and biofilm formation drive hemodialysis catheter-related bloodstream infections, detailing key virulence mechanisms of major pathogens and evaluating emerging surface modification technologies that aim to prevent catheter colonization, while emphasizing ongoing challenges in biocompatibility, durability, and clinical translation.

Watanabe A, Tawada Y, Moriyama M, Doi Y, Suzuki M. Carriage of hypervirulent and ESBL-producing Klebsiella pneumoniae complex among community-dwelling individuals in Japan. Appl Environ Microbiol. 2026 Jan 14. doi:10.1128/aem.01687-25

  • Summary: This community-based genomic study in Japan shows that gut carriage of the Klebsiella pneumoniae complex is common among healthy individuals, predominantly involving K. pneumoniae and K. variicola, while hypervirulent and ESBL-producing strains are rare, suggesting that healthcare settings rather than the community are the main reservoirs for high-risk clones.

Gibbon MJ, Couto N, Cozens K, Habib S, Cowley L, Aanensen DM, et al. Convergence and global molecular epidemiology of Klebsiella pneumoniae plasmids harbouring the iuc3 virulence locus: a population genomic analysis. Lancet Microbe. 2026 Jan 6. doi:10.1016/j.lanmic.2025.101236

  • Summary: This large One Health population genomics study reveals extensive global diversity and frequent hybridisation of iuc3-carrying plasmids in Klebsiella pneumoniae, particularly in animal and environmental settings, demonstrating how resistance and virulence traits can converge outside hospitals and identifying a clinically associated plasmid group in Asia that warrants targeted surveillance.

Host Factors in Infection

Velez AZ, Radin JN, Kennedy EN, Conlon BP. The innate immune protein calprotectin ablates the bactericidal activity of β-lactam antibiotics. Proc Natl Acad Sci U S A. 2026 Jan 14;123(3):e2513462123. doi:10.1073/pnas.2513462123

  • Summary: This study uncovers a host-driven mechanism of antibiotic tolerance in which the immune protein calprotectin reduces the efficacy of β-lactam antibiotics by sequestering zinc and inactivating bacterial autolysins, showing that host-mediated metal limitation at infection sites can critically influence treatment outcomes.

Diagnostics

Gaja-Lachman S, Visser-Timmermans M, Langerak D, Jansma A, Yusuf E. From compliance to complexity: the impact of In-vitro Diagnostic Regulation for clinical microbiology laboratories. Clin Microbiol Infect. 2026 Jan 19. doi:10.1016/j.cmi.2026.01.005

  • Summary: This laboratory-based analysis quantifies the potential impact of the European IVDR on clinical microbiology testing, showing that while many high-volume tests are CE-IVD labelled, laboratories remain heavily reliant on laboratory-developed tests, underscoring the need for a balanced regulatory implementation that ensures compliance without compromising diagnostic capacity.

Marques AR, Ng S-P, McCarthy JE, Telford SR III, Dardick K, Wormser GP, et al. Xenodiagnosis to search for Borrelia burgdorferi after antibiotic treatment of Lyme disease: a prospective cohort study. Clin Infect Dis. 2026 Jan 21;ciag031. doi:10.1093/cid/ciag031

  • Summary: This xenodiagnosis study found no evidence that Borrelia burgdorferi persists in patients after standard antibiotic treatment for Lyme disease, regardless of ongoing symptoms, indicating that xenodiagnosis is unlikely to be useful for detecting persistent infection in humans.

Rosen EA, Krantz EM, Thibodeau A, Kennedy K, Yoke LH, Tverdek F, et al. Diagnostic yield of repeat blood cultures and risk factors for bloodstream infection in persistent febrile neutropenia. Clin Infect Dis. 2026 Jan 20;ciag014. doi:10.1093/cid/ciag014

Improving Clinical Research

Jia Y, Jiang Y, Wu P, Yun Q, Wu H, Yang Z, et al. Impact of study hypotheses on results from randomized clinical trials: comparison between standard and noninferiority randomized clinical trials. Ann Intern Med. 2026 Jan 27. doi:10.7326/ANNALS-25-01344

  • Summary: This meta-research analysis demonstrates that standard randomized clinical trials with positive hypotheses tend to report larger treatment effects than noninferiority trials, especially when blinding is inadequate, suggesting that researchers’ hypotheses can bias published trial results.

Gatti M, Pea F. Real-world evidence and multidrug resistant infections: how can we leverage RWE to improve patient outcome with the novel beta-lactam and beta-lactam/beta-lactamase inhibitor combinations. Infect Drug Resist. 2026 Jan 20; doi:10.2147/IDR.S541584

  • Summary: This review critically examines how evidence from pivotal trials and growing real-world data inform the optimal clinical use of novel beta-lactams and beta-lactam/beta-lactamase inhibitor combinations for multidrug-resistant Gram-negative infections, proposing susceptibility- and resistance-guided therapeutic algorithms and highlighting emerging roles for newer agents across ESBL-producing Enterobacterales, carbapenemase- and metallo-beta-lactamase-producing pathogens, and carbapenem-resistant Acinetobacter baumannii.

Kahana BC, Devane D. Estimands: what they are and why we should use them. J Clin Epidemiol. 2026 Jan;189:112054. doi:10.1016/j.jclinepi.2025.112054

  • Summary: This educational review explains the estimand framework and strategies for handling intercurrent events in clinical trials, showing how different estimand choices directly influence trial design, analysis, interpretation, and relevance of results.

Hamasaki T, He Y, Wu Q, Anderson J-H, Boucher H, Doernberg S, et al. The DOOR methodology: analysis of the DOOR outcomes. 2025 Nov 19

  • Summary: This article argues for patient-centered benefit–risk evaluation in clinical trials and introduces the desirability of outcome ranking (DOOR) framework as a method to better capture overall patient outcomes and treatment effect heterogeneity beyond traditional single-endpoint analyses.

General Interest

Nseir S, Salluh JIF, Póvoa P. Update on infection: from prevention to diagnosis and management. Intensive Care Med. 2026 Jan 22; doi:10.1007/s00134-025-08285-2

  • Summary: Reviews 15 influential infection studies from 2025, showing limited benefit of adjunctive therapies and rapid diagnostics for improving survival, modest reductions in antibiotic duration with biomarker-guided stewardship, and mixed success of strategies to optimize antimicrobial use and prevent hospital-acquired infections.

Riva MA. The clinical thermometer as the first home test for infectious disease. Clin Infect Dis. 2026 Jan 21; doi:10.1093/cid/ciag030

  • Summary: Argues that home diagnostic tests historically function better as tools for individual disease management than for population-level public health screening, and proposes the clinical thermometer as the earliest and most enduring example of domestic testing.

Dewidar O, Akl EA, Morgano GP, Parmelli E, Saz-Parkinson Z, Langendam MW, et al. GRADE guidance: update on developing good practice statements in guidelines. Ann Intern Med. 2026; doi:10.7326/ANNALS-25-00431

  • Summary: Provides updated GRADE guidance on developing good practice statements, clarifying their definition, categorization, and operationalization, and introducing a new tool to improve transparency, consistency, and trustworthiness of clinical guidelines.

Groarke EM, Turturice B, Patel BA, Quinn KA, Fike A, Grayson PC. VEXAS syndrome: a comprehensive review of pathogenesis, clinical spectrum, and therapeutic strategies. Lancet. 2026 Jan 8; doi:10.1016/S0140-6736(25)02164-6

  • Summary: Describes VEXAS syndrome as a late-onset, male-predominant autoinflammatory disease caused by somatic UBA1 mutations, characterised by refractory inflammation and bone marrow failure, with limited treatment options beyond glucocorticoids and selected targeted or curative therapies.

Freiberg JA, Wright PW. What’s hot this year in ID clinical science 2025. Clin Infect Dis. 2026 Jan 9; doi:10.1093/cid/ciaf740

  • Summary: Highlights major advances in infectious diseases research in 2025, including new antibiotics and innovative technologies, while emphasizing that the resurgence of measles illustrates how gains can be rapidly undermined without sustained public health commitment.

Kirchhelle C, Alas Portillo MY, Davis MDM, Doron A, Dreser A, Fortané N, et al. (Un)intended consequences: a social sciences stocktake of a decade of Global Action Plan-inspired antimicrobial governance. Lancet Microbe. 2026 Jan 14; doi:10.1016/j.lanmic.2025.101315

  • Summary: Critically examines global antimicrobial resistance governance since 2000, showing that while investment and action increased, neglect of social, equity, and local contextual factors has limited impact, prompting calls for more people-centred and integrated approaches in future policies.

Lajaunie AM, Patel B, Malani PN. Fever, rash, and dizziness in a 32-year-old. JAMA. 2026 Jan 14; doi:10.1001/jama.2025.24574

  • Summary: Presents a clinical case of a transgender woman with fever, annular rash, and exertional dizziness associated with bradycardia, illustrating the importance of integrating symptom chronology, dermatologic findings, and cardiac signs in infectious disease diagnosis.

Durand ML, Siedner MJ, Chen JW, Rossin EJ, Rosen DA, Klontz EH. Case 2-2026: a 63-year-old man with pulmonary nodules, liver mass, and vision loss. N Engl J Med. 2026 Jan;394:282-294. doi:10.1056/NEJMcpc2402495

  • Summary: Reports a complex diagnostic case of a man with fever, pulmonary nodules, liver mass, brain lesions, and visual loss, underscoring the role of systematic evaluation in identifying disseminated infectious or inflammatory disease.
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