Journal of Microbiology Immunology and Infection最新文献

Background: Mycobacterium kansasii complex (MKC) is the second common slowly growing mycobacterium associated with pulmonary diseases, typically presenting as chronic, progressive respiratory symptoms with structural lung damage. This study aimed to identify the prognostic factors, genotypes, antimicrobial susceptibility, and treatment outcomes in patients with MKC pulmonary disease (MKC-PD).

Methods: This retrospective cohort study of patients with MKC-PD from January 2016 to August 2021 was conducted at Linkou Chang Gung Memorial Hospital in Taiwan. Diagnosis was based on the 2020 American Thoracic Society/European Respiratory Society/European Society of Clinical Microbiology and Infectious Diseases/and Infectious Diseases Society of America criteria. Medical records were reviewed for demographic data, antimycobacterial agents, and treatment outcomes. Speciation was based on heat-shock protein 65 (hsp65) or Tu elongation factor (tuf) gene sequencing for MKC. Antimicrobial susceptibility was determined using Sensititre RAPMYCO2 broth microdilution.

Results: A total of 202 isolates, one from each patient, were included in the analysis. Sixty-six patients did not meet the diagnostic criteria for MKC-PD, and 71 underwent clinical monitoring without antimycobacterial therapy. Of 65 treated patients, 30 (46.2 %) achieved treatment success, whereas 35 (53.8 %) were categorized as treatment failure. Logistic regression analysis identified age, body mass index (BMI), and treatment duration as significant predictors of treatment outcomes. Of 33 rifampin-resistant strains, 21(63 %) were identified as Mycobacterium persicum.

Conclusions: In this cohort of patients with MKC-PD, treatment outcomes were significantly associated with age, BMI, and treatment duration. These findings underscored the importance of early individualized risk stratification to improve treatment outcomes in MKC-PD.

Background: The increasing incidence of multidrug-resistant Enterobacteriaceae (MDRE) presents a significant challenge in clinical settings. We aimed to evaluate the impact of antimicrobial stewardship interventions (ASIs) on clinical outcomes in patients with MDRE bloodstream infections (BSI).

Materials and methods: A single-center, pre-post quasi-experimental study was conducted on patients with BSIs caused by MDRE from March 1, 2014 to February 29, 2016. Infectious disease specialists actively reviewed all positive blood culture notifications and provided evidence-based recommendations for antibiotic therapy. The primary outcomes were 30-day mortality and time to appropriate antibiotics. Secondary outcomes included the hospital length of stay (LOS) after BSIs and duration of antibiotic therapy among survivors.

Results: Total 193 patients were included: 73 patients in the pre-intervention period and 120 patients in the intervention period. The 30-day mortality was lower in the intervention group (12.5% vs. 28.8%, P = 0.007). Species identification of BSI pathogens was more rapidly completed (median 70 h vs. 76 h, P = 0.001), and the time to appropriate antibiotics (median 9 h vs. 33 h, P < 0.001) and duration of antibiotic therapy (10 days vs. 12.5 days, P < 0.001) were shorter in the intervention group. Cox regression analysis revealed that ASIs were associated with a better prognosis among adults with MDRE BSIs (hazard ratio: 0.40; 95 % CI: 0.20-0.77; P = 0.006).

Conclusion: ASIs can reduce the time to appropriate antimicrobial therapy, shorten antibiotic therapy duration, and improve clinical outcomes in patients with BSIs caused by MDRE.

Background: Although high-dose daptomycin (≥8 mg/kg) and linezolid are recommended treatments for vancomycin-resistant Enterococci (VRE) bloodstream infection (BSI), direct comparisons and the impact of achieving prespecified pharmacokinetic/pharmacodynamic (PK/PD) target on outcomes remain unclear.

Methods: We conducted a retrospective observational study in a single health system (January 2010-December 2021). Patients receiving daptomycin ≥8 mg/kg or linezolid for VRE BSI were included. The primary outcome was in-hospital mortality. The free area under the concentration-time curve to minimum inhibitory concentration ratio (fAUC/MIC) was estimated to assess its association with outcomes.

Results: Overall, 795 patients met the inclusion criteria. The overall mortality was 59.2 %. The linezolid group (n = 170) had a mortality of 44 %, and the daptomycin group (n = 625) mortality was 63 % (P < 0.001). Among daptomycin-treated patients, 528 had fAUC/MIC data and 114 achieved the PK/PD target. Mortality was 66 % for fAUC/MIC ≤75.07 (P < 0.001) and 49 % for fAUC/MIC >75.07 (P = 0.41), compared with linezolid group. In multivariable analysis, daptomycin was associated with higher mortality than linezolid (adjusted odds ratio [aOR], 2.00; P < 0.001). However, failing to achieve PK/PD target conferred significantly higher mortality than linezolid (aOR, 2.51; P < 0.001), whereas achieving the PK/PD target showed no difference (aOR, 0.97; P = 0.91).

Conclusions: Even at doses ≥8 mg/kg, the efficacy for daptomycin is comparable to linezolid only when the PK/PD target is reached. Failing to achieve PK/PD target leads to worse outcomes, underscoring the importance of dose optimization and therapeutic drug monitoring.

Background: Mycobacterium tuberculosis (Mtb) infection triggers oxidative stress, necessitating host mechanisms to maintain redox balance. The NADPH oxidase (NOX) family, which produces reactive oxygen species, plays an integral part in this process. While the protective role of NOX2 in Mtb infection is well-studied, the function of NOX4 remains unclear.

Methods: To investigate the impact of NOX4, we infected C57BL/6 wild-type (WT) and NOX4-deficient (Nox4^-/-) mice with the Mtb K strain, assessing bacterial burdens, lung pathology, and immune responses. Then, we analyzed cytokine production and signaling pathways to explore the interaction between dendritic cells (DCs) and T cells.

Results: Nox4^-/- mice exhibited reduced bacterial burden and milder lung pathology compared to WT mice, accompanied by increased DC infiltration and a higher frequency of CD4⁺ T cells of the Th1 subset that secrete interferon-gamma (IFN-γ) in the lungs. Interestingly, ex vivo experiments showed no significant difference in IFN-γ production by T cells from WT and Nox4^-/- mice when activated using antibody-coated beads. However, Mtb-infected bone marrow-derived DCs (BMDCs) from Nox4^-/- mice markedly enhanced IFN-γ production in WT T cells. Further investigation into the role of NOX4 in DCs revealed that BMDCs from Nox4^-/- mice infected with Mtb produced significantly higher levels of IL-12. This elevation was attributed to enhanced activation of IRF1, mediated by the AKT/GSK-3β signaling pathway.

Conclusion: NOX4 negatively regulates IL-12 production in Mtb-infected DCs, suppressing Th1-mediated immunity. Its absence enhances Th1 responses, improves immune control of Mtb. Targeting NOX4 may improve tuberculosis outcomes by strengthening host immunity.

Background: Mycobacterium abscessus (MABS) is a clinically significant nontuberculous mycobacterium, and its drug resistance poses substantial therapeutic challenges. Comprehensive genomic and phenotypic analyses are essential for elucidating the mechanisms underlying this resistance and enhancing understanding of its epidemiology.

Methods: Whole-genome sequencing (WGS) using the Illumina platform was conducted on 61 clinical MABS isolates obtained from patients in Thailand. MABS subspecies classification was performed using FastANI, TYGS, and NTM-Profiler. Phenotypic drug susceptibility testing (pDST) was determined using a broth microdilution method. Resistance mutations were identified through NTM-Profiler and Snippy pipelines.

Results: The analysis classified MABS isolates into three subspecies: subsp. abscessus (40/61, 65.57 %), subsp. massiliense (15/61, 24.59 %), and subsp. bolletii (6/61, 9.83 %). Phylogenetic analysis revealed genetic diversity among the majority of the MABS clinical isolates. These isolates clustered into distinct clades, separate from globally recognized clinical strains and dominant circulating clones. Inducible clarithromycin resistance was detected in 60.66 % of MABS isolates, associated with the T28 variant in erm(41). The Ile80Val mutation in erm(41) was significantly associated with inducible clarithromycin resistance (χ² = 12.61, p < 0.001). Acquired clarithromycin resistance associated with rrl mutations (A2270C, A2270G, A2271C) and amikacin resistance linked to the rrs mutation A1375G were detected in 11.48 % and 4.92 % of isolates, respectively. The categorical agreement between WGS-based DST and pDST was 95.08 %, 88.33 %, and 96.43 % for inducible clarithromycin, clarithromycin, and amikacin, respectively.

Conclusion: This study provides valuable insights into the genomic diversity and antimicrobial resistance of MABS isolates in Thailand, emphasizing regional variations in dominant clones and resistance mechanisms.

Background/purpose: Herpes simplex virus type 1 (HSV-1) is highly prevalent in immunocompromised patients. Due to the recurrent nature of HSV-1 infection, frequent exposure to antiviral agents raises concerns about drug resistance. This study aimed to investigate antiviral-resistant profiles of HSV-1 and discuss the clinical impact of acyclovir-resistant (ACV-R) compared to acyclovir-susceptible (ACV-S) HSV-1 infected patients.

Methods: Repeated sampling specimens during 2010-2023 from all age groups were collected and only those with clinical correlations were illegible to be assessed. Plaque reduction assay and Sanger sequencing were used to determine phenotypic and genotypic profiles (UL23/UL30 genes) of ACV-R HSV-1 isolates, respectively.

Results: A total of 29 HSV-1 isolates from 18 patients, mainly with hematologic disorders (n = 14, 77.8 %) and the clinical diagnosis of orolabial diseases (n = 14, 77.8 %), were analyzed. The prevalence of ACV-R HSV-1 isolates was 69.0 % (20/29). Most isolates were exposed to antiviral agents before sampling (21/29, 72.4 %). There was no statistical difference in treatment response and duration between patients infected with ACV-S and ACV-R isolates (p = 0.274). No strong correlation could be observed between point mutations, 50 % effective concentration value, and previous antiviral exposure duration. Novel mutations E676K and P355S were detected and probably associated with ACV resistance.

Conclusions: The prevalence of ACV-R HSV-1 was higher than reported data from the literature. Several novel mutations were discovered and could enrich the ACV-R HSV-1 database. Further studies are needed to investigate ACV resistance in other potentially related genes, such as UL5 and UL42.

Background: The new nomenclature of steatotic liver disease (SLD) was proposed in June 2023. The effects of cardiometabolic risk factors (CMRFs) on liver-related events (LREs) in patients achieving chronic hepatitis C (CHC) eradication are unknown.

Methods: This study recruited 1185 patients cured of CHC. CMRFs and alcohol consumption were clearly defined. Variables obtained at 12 or 24 weeks after direct-acting antiviral therapy (PW12) were used to identify the predictors of LREs.

Results: A total of 562 patients (47.4 %) had metabolic dysfunction-associated SLD (MASLD), 96 (8.1 %) had MASLD with increased alcohol intake, 14 (1.2 %) had alcohol-related liver disease, 78 (6.6 %) had cryptogenic SLD, and 435 (36.7 %) had no SLD. Multivariable Cox regression analysis indicated that age, alcohol consumption, per CMRF (hazard ratio: 1.332, 95 % confidence interval: 1.094-1.621), posttreatment albumin level, alpha-fetoprotein level, and fibrosis-4 index >3.25 were independent predictors of LREs. Another multivariable analysis revealed that prediabetes and diabetes mellitus were predictors of LREs.

Conclusions: The new fatty liver disease nomenclature of SLD was used to stratify the risk of LREs in patients achieving CHC eradication. The risk of LREs increased by 33 % per CMRF, and prediabetes or DM was a predictor of LREs.

Research background: Traditionally seen as an environmental bacterium, Acinetobacter parvus has rarely been studied in clinical settings. Its role in human infections remains unclear, particularly in vulnerable populations. This study explores its biological traits, antibiotic resistance, and genomic features through the first systematic analysis of strain ZDL0830, isolated from an immunocompromised patient with an abscess.

Research methods: The strain was identified using MALDI-TOF MS and 16S rRNA sequencing. Its growth characteristics, Gram staining, and biochemical properties were analyzed with API 20NE and VITEK 2. Antibiotic susceptibility was tested across multiple drug classes using disk diffusion, Etest, and AutoMic i600. Whole-genome sequencing provided insights into its genetic makeup, with resistance and virulence genes identified through the CARD and VFDB databases. Phylogenetic relationships were assessed using 16S rRNA sequencing and ANI/DDH analysis.

Key findings: The strain exhibited slow growth (visible colonies after 72 h) and limited metabolic activity but shared core pathways with other Acinetobacter species. It was susceptible to β-lactams (e.g., cefoperazone/sulbactam, meropenem) and aminoglycosides (amikacin), but resistant to ciprofloxacin and intermediately resistant to levofloxacin. Genomic analysis revealed only one resistance gene (APH_3-VIa) and virulence factors associated with biofilm formation (lpxC, bfmR) and motility (pilT, gspE1).

Conclusion: This study sheds light on the clinical potential of Acinetobacter parvus, particularly in immunocompromised patients. While its low resistance profile allows for effective treatment, its ability to cause infections warrants further attention.

Background: Therapeutic options for hospitalized people with COVID-19 remain limited, especially for people with non-severe COVID-19 at risk of progression. The anti-inflammatory role of maraviroc, a CCR5 antagonists, makes it a good candidate for therapeutic strategies for COVID-19.

Methods: This was a proof-of-concept, phase II, parallel, open label clinical trial, to evaluate the safety and efficacy of maraviroc (300 mg, bid), CCR5 antagonist, combined with standard of care (SoC) treatment compared to SoC alone during 14 days, in hospitalized people with mild COVID-19 with pneumonia and ambient air oxygen saturation >94 %. Demographical, clinical, and analytical data were assayed at day 0, 7, 14 and 28.

Results: Thirty-three participants were included, 17 in the control and 16 in the maraviroc group. The proportion of participants who experienced COVID-19 progression was 2.8 times higher in the control group than in the maraviroc group, with three participants admitted in intensive care unit versus none in the maraviroc group. The only variable associated with the time to severe COVID-19 progression was maraviroc treatment. The median time on oxygen therapy was 11 days in the control group, while the two participants in the maraviroc group had oxygen therapy for one and four days. Grade 3-4 events were only present in the control group. Maraviroc treatment was associated with a better neutrophil/lymphocyte ratio and lactate dehydrogenase, IL-6 and TNF-α levels at day 7.

Conclusions: We observed a beneficial role of maraviroc in hospitalized participants with mild COVID-19 at risk of progression at admission.