PURPOSE:Among various carbapenemase-producing Enterobacterales (CPE), strains producing metallo-β-lactamases (MBLs)-particularly New Delhi MBL (NDM)-exhibit the most severe resistant phenotypes. This study aimed to identify effective antibiotics or non-antibiotic agents against MBL-producing Enterobacterales. METHODS:An extensive literature search of Google Scholar and the PubMed database was conducted for articles published during 2010-2025 using the search terms (novel antibiotics OR phage) AND (MBL) AND (Enterobacterales OR Enterobacteriaceae). RESULTS:Cefiderocol exhibited lower susceptibility rates compared to aztreonam-avibactam against NDM-producing Enterobacterales isolates according to the 2025 European Committee on Antimicrobial Susceptibility Testing guidelines. Among novel β-lactamase inhibitors, taniborbactam (TAN), xeruborbactam (XER), zidebactam (ZID), and ANT2681 have demonstrated activity against MBLs. Nacubactam (NAC), when combined with partner β-lactams, is active in vitro against CPE isolates harboring blaNDM genes. TAN, XER, ZID, NAC, and ANT2681 are being developed in combination with meropenem, or cefepime for the treatment of infections caused by CPE, including various MBL producers. Additionally, due to the availability of both oral and parenteral formulations, regimens such as XER paired with ceftibuten or tebipenem are currently under evaluation for the treatment of infections caused by serine carbapenemase- and MBL-producing Enterobacterales. Moreover, the novel monobactam LYS228 alone has also demonstrated good in vitro potency against MBL producers. Novel polymyxin derivatives-including SPR741 (combined with mecillinam), SPR206, and QPX9003-and bacteriophages have shown promising activity against MBL-producing Enterobacterales. CONCLUSIONS:Continued monitoring of resistance trends and the development of innovative therapeutic strategies is warranted in the ongoing battle against CPE harboring blaMBL.

We evaluated cefiderocol activity against carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Acinetobacter baumannii (CRAB), characterized the β-lactamase gene profiles of cefiderocol-nonsusceptible CRPA by metallo-β-lactamase (MBL) subtype, and assessed cross-resistance with comparator agents. Cefiderocol minimum inhibitory concentrations (MICs) for 890 CRPA and 1,063 CRAB isolates from the 2024 Antimicrobial Testing Leadership and Surveillance (ATLAS) program were determined by broth microdilution using iron-depleted cation-adjusted Mueller-Hinton broth. Cefiderocol nonsusceptibility was defined as MIC ≥ 8 mg/L per CLSI (intermediate + resistant). DTRPA was defined as nonsusceptible to all anti-pseudomonal β-lactams and fluoroquinolones; DTRAB was defined as nonsusceptible to carbapenems, ampicillin-sulbactam, and fluoroquinolones, reflecting species-specific susceptibility panels. CRPA isolates underwent molecular screening for blaNDM, blaVIM, blaIMP, serine carbapenemase, and ESBL genes; genotype data were not available for A. baumannii. Cefiderocol susceptibility was 93.9% for CRPA and 88.5% for CRAB, respectively (nonsusceptibility 6.1% and 11.5%, respectively; OR = 2.01, P < 0.001); nonsusceptibility among DTRPA and DTRAB was 8.1% and 11.7%, respectively. Among 54 cefiderocol-nonsusceptible CRPA, 41 (76%) harbored no detectable carbapenemase gene. Nonsusceptibility among MBL-positive CRPA was exclusively attributable to blaNDM producers (27.7%, 13/47); blaVIM-positive (n = 68) and blaIMP-positive (n = 21) isolates were uniformly susceptible. Among cefiderocol-nonsusceptible CRPA, 98.1% were co-resistant to ceftazidime-avibactam and 96.3% to ceftolozane-tazobactam.

BACKGROUND:Dengue infection frequently causes thrombocytopenia and bleeding complications. Patients with cardiovascular disease who receive antiplatelet or anticoagulant therapy represent a clinically challenging population during acute dengue infection. Data regarding clinical outcomes and platelet recovery in these patients remain limited. METHODS:This observational study included a single-center retrospective cardiovascular dengue cohort and an exploratory platelet-monitoring cohort. In the retrospective cohort, patients were classified according to pre-existing antithrombotic therapy (ATT) at dengue diagnosis: no antithrombotic therapy (No ATT), single antiplatelet therapy (SAPT), dual antiplatelet therapy (DAPT), or oral anticoagulant therapy (OAC). Major bleeding was assessed within 7 and 30 days after dengue diagnosis. In the exploratory platelet-monitoring cohort, serial platelet count and platelet function were assessed during dengue illness. RESULTS:The retrospective cohort included 1,693 patients (No ATT, n = 1,493; SAPT, n = 163; DAPT, n = 22; OAC, n = 15). ATT users were older and had a greater burden of cardiovascular comorbidities and more frequent severe dengue manifestations. The observed 7-day major bleeding rates in the No ATT, SAPT, DAPT, and OAC groups were 0.34%, 0.61%, 4.55%, and 6.67%, respectively (P = 0.011), with corresponding 30-day rates of 1.15%, 1.84%, 9.09%, and 13.33% (P = 0.002). In the exploratory platelet-monitoring cohort (6 non-antiplatelet users and 2 aspirin users), aspirin users had a longer platelet count nadir-to-recovery time than non-antiplatelet users [median (IQR), 7.5 (6.0-9.0) vs 4.0 (3.75-4.25) days; P = 0.04] and a longer interval from the lowest platelet function value to recovery [median (IQR), 9.5 (8.0-11.0) vs 4.0 (3.75-4.25) days; P = 0.04]. CONCLUSIONS:Pre-existing ATT users had a greater comorbidity burden and more severe dengue manifestations. SAPT users showed similar observed short-term major bleeding rates to patients without ATT. Exploratory monitoring suggested delayed platelet count and function recovery among aspirin users.

OBJECTIVES:Viral rebound has emerged as a virologic characteristic. The study aimed to explore its determinants and impact on clinical outcomes. METHODS:The study included adults hospitalized for COVID-19 at a tertiary hospital in Taiwan from January to December 2022. Viral rebound was defined as a ≥ 5-unit decrease in RT-PCR Ct values or a new positive antigen test after tested negative within 10-30 days of diagnosis. The primary outcome was viral rebound, and secondary outcomes included 30-day mortality and in-hospital overall mortality. RESULTS:Among 353 patients, 46 (13%) developed viral rebound. Patients with viral rebound exhibited longer hospitalization [25 days (IQR: 16-37) vs. 17 days (IQR: 12-28), p=0.013], higher 30-day mortality (21.7% vs. 9.8%, p=0.017) and overall mortality (28.3% vs. 16.3%, p=0.048). Systemic dexamethasone use for initial COVID-19 was independently associated with increased risk of viral rebound (adjusted odds ratio [aOR], 1.99; 95% CI, 1.06-3.75, p=0.034). In the landmark restricted to those who were alive at day 10 after diagnosis, viral rebound (aOR, 2.56; 95% CI, 1.11-5.88, p=0.027) was an independent predictor of 30-day mortality. CONCLUSIONS:Viral rebound was associated with prolonged hospitalization and increased 30-day mortality, underscoring the need for enhanced clinical monitoring.

Rationale & Objective Hemodialysis (HD) patients are susceptible to severe illness and mortality from COVID-19. We investigated immunogenicity following bivalent vaccines containing ancestral and omicron variant (BA.1 or BA.4/BA.5) antigens in HD patients. Study Design a prospective observational cohort study Setting & Participants We enrolled adult HD patients and age-matched healthy adults between October 2022 and February 2023. Blood samples were taken at baseline, one month(M1) and three months(M3) post-vaccination. Exposures bivalent mRNA vaccines Outcomes Anti-SARS-CoV-2 spike protein receptor-binding domain antibodies, surrogate viral neutralization tests (sVNT), pseudovirus neutralization tests (PVNT) and SARS-CoV-2-specific interferon-γ release assay(IGRA) Analytic Approach Student’s t-test, Mann-Whitney U test or Kruskal-Wallis test with Dunn's post-hoc test for continuous variables; chi-square test or Fisher exact test for categorical variables. Holm-Bonferroni correction was applied for multiple comparisons. Results Among 106 HD patients, 89.6% and 10.4% received either Spikevax Original/Omicron BA.1 or BA.4/5. Prior SARS-CoV-2 infection was documented in 25.5%, and 93.4% had received four monovalent vaccine doses. Anti-SARS-CoV-2-S antibody levels demonstrated a 4.2-fold increase at M1, subsequently declining by 50% at M3. sVNT revealed enhanced neutralization against Omicron BA.1, BA.2, and BA.4/5, with seropositive rates of 75.3-96% maintained at M3. Infection-naïve patients exhibited lower baseline antibodies but demonstrated more pronounced booster responses compared to previously infected individuals. PVNT demonstrated 2-to-9.9-fold increases at M1 in neutralizing capacity against emerging Omicron subvariants BF.7, BA.2.75, BQ.1.1, and XBB.1.5. However, only 58.1% of patients demonstrated positive IGRA responses at M1, with no correlation to humoral outcomes. Immune responses were comparable between HD patients and healthy controls. Limitations Limited sample size, heterogeneous vaccination and infection history Conclusions Bivalent mRNA vaccines significantly enhanced antibody titers and broadened neutralizing capacity against emerging Omicron subvariants in HD patients. However, cellular immunity remained suboptimal despite multiple antigen exposures, highlighting the need for optimized vaccination strategies in this immunocompromised population.

Background:Asymptomatic Clostridioides difficile colonization (CdC) serves as a reservoir for pathogen transmission and may precede clinical infection. While risk factors for CdC have been well described in hospitalized populations, community-based data-particularly regarding lifestyle-associated factors and gut microbiota alterations-remain limited in Taiwan. This study aimed to determine the prevalence and risk factors of community-acquired CdC and to explore associated gut microbiota differences. Materials and Methods:We conducted a cross-sectional study analyzing 250 residual stool samples from adults aged ≥40 years who participated in community health screenings in Tainan City between 2006 and 2009. CdC was detected by polymerase chain reaction targeting the triosephosphate isomerase (tpi) gene. Demographic characteristics, lifestyle factors, and laboratory parameters were collected and analyzed. Exploratory 16S rRNA gene sequencing was performed on selected samples to compare gut microbiota composition between CdC and non-CdC groups. Results:The prevalence of CdC was 11.6% (29/250). Cigarette smoking was identified as the sole independent factor associated with CdC (adjusted OR 2.35, 95% CI 1.05-5.28; P = 0.038). Exploratory microbiota analysis revealed differences in community composition between CdC and non-CdC samples, including increased relative abundance of Proteobacteria in CdC. Conclusion:Cigarette smoking was associated with an increased likelihood of community-acquired CdC in southern Taiwan. Distinct gut microbiota profiles were observed in individuals with CdC, supporting a potential link between smoking-related microbiota alterations and susceptibility to asymptomatic colonization. These findings underscore the relevance of modifiable lifestyle factors in the epidemiology of community CdC and warrant further investigation.

BACKGROUND:Long-term care facilities (LTCFs) are highly vulnerable to healthcare-associated infections, yet evidence evaluating policy-driven, incentive-based infection prevention and control (IPC) programs in these settings remains limited. METHODS:We conducted a retrospective policy evaluation using routinely collected on-site audit and administrative data from 59 LTCFs participating in the "2025 Taichung City On-site Inspection Program for Incentives to Strengthen Infection Control in Long-term Care Facilities". Facilities were assessed using standardized IPC indicators, including mandatory core indicators (Indicators 1-3) and voluntary incentive-based indicators (Indicators 4-6). Outcomes included indicator-level compliance, incentive qualification, reward distribution by facility type and bed-capacity category, and the results of post-audit appeals. RESULTS:Compliance with mandatory core IPC indicators was consistently high: all facilities met Indicator 1 (100%), and 58 facilities complied with Indicators 2 and 3 (both 98.3%). In contrast, non-compliance was more frequently observed among incentive-based indicators. Although 34 (57.6%) facilities applied for Indicator 4 and 48 (81.4%) for Indicator 5, non-compliance occurred in 8.8% and 4.2% of applicants, respectively. Indicator 6 demonstrated the greatest implementation gap, with 13 (76.5%) of 17 applicant facilities classified as non-compliant, primarily due to ineligibility of certified personnel. All nine appealed audit items were approved after review. Overall, 58 facilities (98.3%) qualified for incentive payments. CONCLUSIONS:A government-led, incentive-based IPC audit program was associated with near-universal compliance with core IPC standards in LTCFs. Linking structured audits, preparedness requirements, and financial incentives represents a feasible approach to strengthening IPC capacity in LTCFs.

OBJECTIVES:To evaluate cefiderocol (FDC) activity against carbapenem-resistant Enterobacterales (CRE) globally, characterize the β-lactamase gene profiles of non-susceptible isolates by metallo-β-lactamase status, and assess alternative agents. METHODS:Cefiderocol minimum inhibitory concentrations for 1657 CRE isolates from the 2024 Antimicrobial Testing Leadership and Surveillance programme were determined by broth microdilution. Isolates underwent molecular screening for carbapenemase, extended-spectrum β-lactamase, and AmpC genes. Between-group differences were assessed using odds ratios (ORs) with Fisher's exact tests. RESULTS:Overall FDC susceptibility rate was 93.1% by Clinical and Laboratory Standards Institute and 80.7% by EUCAST criteria, respectively. Non-susceptibility varied substantially by genus: Escherichia spp. 25.3%, Providencia spp. 14.0%, Enterobacter spp. 12.5%, and Klebsiella spp. 3.5%. FDC non-susceptibility rates revealed further heterogeneity within genera; notably, Enterobacter cloacae (23.1%) and Enterobacter kobei (50.0%) had substantially higher non-susceptibility than Enterobacter hormaechei (7.2%), and Providencia rettgeri (22.2%) exceeded Providencia stuartii (8.0%). Asia had the highest unadjusted non-susceptibility rate (10.5%; OR 4.73, P = 0.002); however, in a multivariable logistic regression adjusting for genus, age, and specimen source, genus was the dominant independent predictor (Escherichia spp. adjusted OR 8.21, 95% confidence interval 4.75-14.17), and the Asia effect was attenuated to a non-significant trend (adjusted OR 3.99, 0.93-17.14, P = 0.063). Among 115 non-susceptible isolates, 51 (44.3%) were metallo-β-lactamase-positive, predominantly blaNDM (94.1%), with high extended-spectrum β-lactamase co-carriage (blaCTX-M 74.5%), while 50 (43.5%) harboured no identifiable carbapenemase gene. CONCLUSIONS:FDC remains active against most CRE globally, although non-susceptibility varies by genus, species and region. Notably, nearly half of non-susceptible isolates lacked detectable carbapenemase genes.

Background Hypervirulent Klebsiella pneumoniae (hvKp) was first identified in Taiwan in 1986, and has emerged as a leading cause of severe community-acquired infections, particularly in Asia. Its metastatic nature, often involving the liver and eyes, poses significant diagnostic challenges and is associated with substantial morbidity. Case presentation A 47-year-old Taiwanese man with poorly controlled diabetes presented with fever, nausea, and blurred vision due to diabetic ketoacidosis, K. pneumoniae bacteremia, and endogenous endophthalmitis. Computed tomography revealed abscesses in the liver, lungs, kidney, and prostate. The isolate was confirmed as a hypervirulent strain (positive string test, K2 serotype, and virulence genes). Despite parenteral ceftriaxone and liver drainage, fever persisted. Gallium-67 scintigraphy localized concentrated inflammatory activity to the prostatic abscesses. This finding guided a definitive transrectal aspiration for source control. The patient completed eight weeks of antimicrobial therapy, transitioned from ceftriaxone to oral ciprofloxacin. Despite prompt systemic and intravitreal antibiotics, the right eye progressed to phthisis bulbi with total loss of light perception. At the 11-month follow-up, the patient remained systemically stable with no recurrence of infection. Conclusion Metastatic infections associated with hvKp frequently extend beyond the classic presentation of liver abscesses and endophthalmitis. Nuclear imaging, specifically Gallium-67 scintigraphy, can be instrumental in detecting occult inflammatory foci that may remain clinically silent. Maintaining high clinical vigilance regarding the diverse and often asymptomatic manifestations of hvKp, such as prostatic abscesses, is vital. Timely diagnostic intervention and aggressive source control are essential to prevent persistent sepsis and improve overall clinical outcomes.

BACKGROUND:Sexually transmitted enteric infections (STEIs) are increasingly recognized among men who have sex with men (MSM), yet contemporary surveillance data from Asia remain limited. We conducted a molecular surveillance study to characterize the burden, clinical features, and associated factors of STEIs among MSM in southern Taiwan. METHODS:Between March 2019 and March 2024, MSM participants were enrolled from several sources, including human immunodeficiency virus outpatient clinics, pre-exposure prophylaxis services, hospitals (for diarrheal illness), and venue-based community outreach programs, regardless of gastrointestinal (GI) symptoms. Stool specimens were tested using multiplex polymerase chain reaction panels targeting enteric pathogens (GI panel) and sexually transmitted pathogens (sexually transmitted infection [STI] panel). Clinical, behavioral, and microbiological data were analyzed to identify factors associated with pathogen detection. RESULTS:Among 565 participants, 107 (19%) reported GI symptoms at the time of testing. Overall, at least one pathogen detected by the GI or STI panel was noted in 107 participants (19%). Regarding STI pathogens, Chlamydia trachomatis and Neisseria gonorrhoeae were detected in 7% and 3% of participants, respectively. Notably, among the C. trachomatis-positive samples, 11 of 38 (29%) were identified as lymphogranuloma venereum (LGV) strains. Among enteric pathogens, Shigella (4%) was most common, followed by Giardia duodenalis (4%) and Entamoeba histolytica (3%). Multivariable analysis showed that detection of rectal LGV (adjusted odds ratio [aOR] 10.8), proton pump inhibitor use (aOR 7.3), rectal N. gonorrhoeae (aOR 6.8), and insertive anal sex (aOR 3.2) were independently associated with GI panel positivity. Shigella was associated with prior syphilis and concurrent Campylobacter detection. Co-detection of enteric and sexually transmitted pathogens was observed in 21% of 107 pathogen-positive participants. CONCLUSION:This study provides comprehensive, molecular surveillance of STEIs among MSM in Asia and reveals a significant burden of frequent co-detection with conventional STIs. Rectal LGV had different co-infection patterns compared with non-LGV genotypes. Our findings highlight the need for integrating enteric pathogen surveillance into comprehensive sexual health frameworks for MSM.

Carbapenem-resistant Enterobacterales (CRE) pose significant treatment challenges. While ceftazidime-avibactam (CZA) is commonly used, resistance rates have been increasing. Aztreonam-avibactam (ATM-AVI) may represent a promising alternative. A total of 109,603 Enterobacterales isolates were collected from 307 sites across 63 countries between 2019 and 2023 as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program. CRE were defined as isolates with a meropenem minimal inhibitory concentration (MIC) ≥2 mg/L. Susceptibility testing was conducted according to the Clinical and Laboratory Standards Institute (CLSI) 2025 guidelines, and β-lactamase genes were identified by multiplex PCR and sequencing. Of the total Enterobacterales isolates, 7,520 (7.6%) were identified as CRE, with Klebsiella species accounting for the majority (76.3%, 5,735/7,520). CZA susceptibility was 49.1% (3,696/7,520), with a significant increase in resistance from 42.1% (540/1,283) in 2019 to 61.0% (875/1,435) in 2023 (P < 0.05). Although CRE prevalence was highest in Asia (12.2%, 2,850/23,295), the highest rate of CZA resistance was observed in Africa/Middle East (73.9%, 557/754). In contrast, ATM-AVI demonstrated the highest in vitro activity, with 97.4% (7,324/7,520) of CRE isolates exhibiting MICs ≤4 mg/L. This activity remained strong against carbapenemase-producing strains, including metallo-β-lactamase (MBL) producers. However, reduced susceptibility was observed in Escherichia (80.2%, 556/693) and Proteus (88.9%, 56/63) species. Notably, resistance to ATM-AVI among carbapenem-resistant Escherichia species was geographically clustered in India, where 9.9% (36/364) of isolates were resistant. In conclusion, ATM-AVI exhibits potent activity against global CRE, including MBL producers, and outperforms other β-lactam/β-lactamase inhibitor combinations. However, emerging resistance in Escherichia and Proteus species-particularly with regional clustering-highlights the importance of continued global surveillance.

OBJECTIVES:To evaluate the prognostic role of initial band percentages in adults presenting to the emergency department (ED) with bacteremia. METHODS:This 8-year retrospective cohort study included treatment-naïve adults with bacteremia who underwent a manual differential hemogram. The primary outcome was 30-day mortality after ED arrival. The association between initial band percentages and mortality was analyzed using a logistic regression model adjusted for independent prognostic factors. RESULTS:Of the total 5558 patients, patients were stratified into five groups by the initial percentage of band cells (neutrophils): 0%-10% (3358 patients), 10%-19% (849), 20%-29% (618), 30%-39% (347), and ≥ 40% (386). The groups varied significantly in terms of clinicodemographic characteristics, bacteremia profiles, and mortality rates at 3, 15, and 30 days. Overall, each 10% increase in the initial band percentage was independently associated with an average 12% increase in 30-day mortality rates. The positive association between initial band percentages and 30-day mortality rates remained consistent across predefined patient subgroups. CONCLUSIONS:A higher initial percentage of band cells is independently associated with a higher risk of short-term mortality in adults presenting to the ED with bacteremia.

OBJECTIVES:Lymphogranuloma venereum (LGV) caused by Chlamydia trachomatis genotypes L1-L3 has been resurging among men who have sex with men (MSM) and people with HIV (PWH) in Western countries. While historically attributed to tropical regions, rectal LGV has been rarely recognised in Asia, with Taiwan recently becoming the second Asian country to report cases. METHODS:A multicentre, laboratory-based surveillance was conducted from January 2020 to December 2023 in Taiwan. Specimens were collected from MSM through syndromic testing and screening of high-risk populations. C. trachomatis was identified using commercial multiplex PCR assays, with genotyping performed through ompA gene sequencing. LGV-positive samples underwent multilocus sequence typing (MLST) following established protocols. RESULTS:Among 446 C. trachomatis-positive samples, 391 (87.7%) underwent successful ompA sequencing. Genovariant L2b accounted for 9.7% of cases, predominantly among PWH with rectal chlamydia (18.2%). PWH accounted for 85.7% of all genovariant L2b cases. Of 38 genovariant L2b samples from 35 cases, 34 (84.2%) samples completed MLST, revealing sequence type (ST) 53 as the predominant strain (74%). ST39 and ST63 were identified as unreported STs in Western countries, along with previously reported ST58. The four identified STs formed a cluster. CONCLUSIONS:Our findings indicate the clonal spread of C. trachomatis L2b-ST53 among MSM in Taiwan, primarily affecting PWH. The predominance of ST53 suggests potential international and domestic spread, indicative of the need for enhanced surveillance.

BACKGROUND:Phenotype-desirable antimicrobial therapy (PDAT) has recently been proposed to improve prognosis in patients with Enterobacterales bacteraemia. However, focusing on overall bacteraemia, the association of prompt PDAT with short-term mortality and the risk of hospital-onset Clostridioides difficile infection (hCDI) remains uncertain. METHODS:Among treatment-naïve adults with community-onset bacteraemia, clinical variables were retrospectively collected. Etiologic pathogens were prospectively preserved to accurately determine the timepoints of effective antimicrobial therapy and PDAT initiation. After stratifying patients into four groups by PDAT delays (<2.0 d, 2.0-5.9 d, ≥6.0 d, and no PDAT), a time-dependent Cos-regression model was used to investigate the association of prompt PDAT with 30-d crude mortality and hCDI development, after, respectively adjusting for the independent predictors identified. RESULTS:Of the total 3815 patients, with the no-PDAT group (n = 195) as the reference, patients with PDAT delays of <2.0 d (n = 1819), 2.0-5.9 d (n = 1197), and ≥6 d (n = 604) were at significantly reduced risks of 30-d mortality and hCDI. For these categories, adjusted hazard ratios for 30-d mortality were 0.32, 0.35, and 0.63, respectively, and those for hCDI were 0.03, 0.19, and 0.44, respectively. Across all subgroups, prompt PDAT was consistently associated with reduced risks of 30-d mortality and hCDI development. CONCLUSIONS:Prompt PDAT was associated with reduced risks of short-term mortality and hCDI. These findings highlight the indispensability of the timely administration of pathogen-targeted narrow-spectrum antimicrobials, particularly in high-risk patients, and support the integration of this strategy into antimicrobial stewardship programmes.

OBJECTIVE:The standard antimicrobial therapy for Clostridioides difficile infections (CDIs) is limited to oral fidaxomicin or vancomycin, but these agents are associated with high treatment failure and recurrence rates. Clostridium butyricum has been proven effective in many types of gastrointestinal disease. Due to its ability to not disrupt the gut microbiota, we hypothesized that the probiotic C. butyricum Miyairi produced bacteriocin (CBMB-B) can be a potential therapeutic agent against CDIs. METHODS:The inhibitory effects of CBM-B and vancomycin were compared using the kinetic time-kill assay, ex vivo co-culture model and mouse model. RESULTS:Among the clinical isolates of C. difficile, the minimal inhibitory concentration (MIC) of CBM-B ranged from 0.0625 to 8 µg/mL; the MIC50 and MIC90 were 1 µg/mL and 4 µg/mL, respectively. In a mouse model where the animals were infected with various C. difficile strains belonging to RT178 and receiving CBM-B intra-rectally, mice infected with isolates with a relatively low CBM-B MICs (2 µg/mL, abbreviated as M2) revealed significant better therapeutic effect, including less loss of body weight and cecum weight, compared with those infected with isolates of relative high CBM-B MICs (4 or 8 µg/mL, abbreviated as M4 or M8). The relative C. difficile bacterial burden in stool of mice receiving CBM-B treatment were significantly lower among mice infected with M2, compared with that infected with M4 or M8. CBMB treatment, compared with vancomycin therapy revealed less disturbance in gut microbiota. CONCLUSION:CBMB-B could be effective in the treatment of CDIs where infections were caused by C. difficile isolates with relative low MICs.

ABSTRACT Commercial antifungal susceptibility tests were available for clinical yeast isolates. However, the updated Sensititre YeastOne (SYO) version YO10C excluded Cryptococcus species for susceptibility testing. Uncorrelation of antifungal susceptibility patterns by SYO and therapeutic outcomes had been recently reported. We compared the performance of current commercial susceptibility tests with the standard CLSI broth microdilution (BMD) method for clinical Cryptococcus isolates. Forty-seven clinical Cryptococcus isolates were included from 1 January 2012 to 30 June 2023, among which 44 isolates were Cryptococcus neoformans while 3 were Cryptococcus gattii. The performance of SYO version YO10C and VITEK2 YS09 was compared with the CLSI BMD method and correlated with MLST analysis and ERG11 mutation detection. Non-wild-type (non-WT) strains to amphotericin B (AMB) were observed in 11 isolates with the CLSI BMD method and 8 with SYO among 44 C. neoformans isolates, but only 1 isolate was classified as non-WT by both methods. Additionally, all C. neoformans isolates were susceptible to AMB with their MIC ≤1 µg/mL according to the clinical breakpoint defined by EUCAST. Non-WT to FLC were observed in 5 C. neoformans isolates with SYO, but they were classified as WT by CLSI BMD and VITEK2. The essential agreements between SYO and CLSI BMD were >90% to most antifungal agents except ITC in C. neoformans isolates (64%) and AMB in C. gattii group (67%). Between SYO and CLSI BMD, the major error (ME) rates were 11% (n = 5) to FLC, 5% (n = 2) to ITC, and 2% (n = 1) to 5FC in C. neoformans isolates, and the very major error to 5FC was found in one C. gattii isolate. ERG11 mutation with identical I199V was detected in 89% (n = 39) C. neoformans isolates, and 97% (n = 38) of them belonged to sequence type (ST) 5. The ERG11 mutation or cryptococcal ST was not associated with a decrease of antifungal susceptibilities. ME of FLC by SYO version YO10C compared to the CLSI BMD method reached up to 11% of C. neoformans isolates. The results of FLC MIC by SYO should be interpreted cautiously and correlated with therapeutic response, and further verification with the CLSI BMD method or VITEK2 is required.IMPORTANCEThe study pointed out the major errors of fluconazole susceptibility results in clinical Cryptococcus neoformans isolates between the commercial Sensititre YeastOne Susceptibility Plate version YO10C and the standard CLSI broth microdilution method. The results should be interpreted carefully with clinical correlation, and a different method of antifungal susceptibility testing should be considered if a discrepancy of susceptibility results is suspected.

BACKGROUND:The prognostic advantage of prompt antimicrobial therapy has been evidenced in patients experiencing bacteremia. When a specific bacteremia-etiologic pathogen is highly suspected or rapidly identified, studies addressing the question of how broad-spectrum antimicrobials should be administered based on local epidemiologic data and antibiograms are limited. OBJECTIVE:To determine the optimal antimicrobial susceptibility to support empirical prescribing decisions. METHODS:In the multicentric cohort study of adults with community-onset monomicrobial bacteremia, bacteremia-causing bacteria were prospectively collected to establish the antibiogram, and clinical information was retrospectively captured. Using Cox regression models after adjusting for independent predictors of mortality, the associations between administering antimicrobials with varied susceptibility categories and 30-day mortality were examined. RESULTS:For overall 5080 patients, significantly higher mortality risks were identified in the categories of <60% (adjusted hazard ratio [AHR], 2.47; p < 0.001), 60-69% (AHR, 1.68; p < 0.001), 70-79% (AHR, 1.55; p = 0.003), and ≥90% (AHR, 1.42; p = 0.03), compared with the reference category of 80-89%. For critically ill individuals, significantly higher mortality risks were disclosed in the categories of <60% (AHR, 2.92; p < 0.001), 60-69% (AHR, 2.17; p < 0.001), 70-79% (AHR, 2.09; p < 0.001), and 80-89% (AHR, 1.80; p = 0.003), compared with the reference category of ≥90% CONCLUSIONS: An optimal susceptibility range of 80-89% for empirical antimicrobial administration was determined to be significantly associated with a reduced risk of mortality. Critically ill patients might require a higher susceptibility threshold of ≥90%.