Background: The contemporary guidelines have recommended multiple antimicrobial therapies along with oral macrolides for the treatment of Mycobacterium abscessus complex lung disease (MABC-LD). However, there is little evidence supporting the parenteral tigecycline-containing regimens against MABC-LD. Therefore, we conducted this study to evaluate the effect of intravenous tigecycline-containing regimens on the treatment of MABC-LD. Methods: A retrospective study was conducted in 6 medical centers. Patients with MABC-LD that were followed up at ≥12 months were enrolled. Mycobacterium abscessus subspecies were identified by hsp65, rpoB, secA1 gene PCR, and sequencing. Antimicrobial susceptibility was determined for 34 patients using broth microdilution methods following the Clinical and Laboratory Standards Institute (CLSI) guideline. The microbiology and treatment outcomes were defined as either success or failure. The impacts of tigecycline and amikacin were adjusted for age, comorbidities, surgical resection, and radiologic scores. Results: During the study period, seventy-one patients were enrolled for final analysis. The microbiology failure rate was 61% (43/71) and the treatment failure rate was 62% (44/71). For M. abscessus complex, 97% (33/34) of tigecycline MIC were ≤1 mg/L. Amikacin also demonstrated great susceptibility (94.1%; 32/34). Treatment with regimens containing tigecycline plus amikacin provided better microbiology success (adjusted OR 17.724; 95% CI 1.227–267.206) and treatment success (adjusted OR 14.085; 95% CI 1.103–166.667). Conclusion: The outcome of MABC-LD is always unsatisfactory. Treatment regimens with oral macrolide in combination with tigecycline and amikacin were correlated with increased microbiology success and less treatment failure.

Mortality rates due to Cryptococcus neoformans var. grubii fungemia remain significant despite treatment with antifungal drugs. The predictive function of antifungal susceptibility and its correlation with treatment outcome remains controversial. A retrospective study was conducted from January 1, 2009, to December 31, 2016, on 85 patients with C. neoformans var. grubii fungemia confirmed by matrix-assisted laser desorption ionization–time-of-flight mass spectrometry. Antifungal drug susceptibility was determined using the YeastONE™ colorimetric broth microdilution method coupled with Vizion™ System following the Clinical and Laboratory Standards Institute guidelines. Six antifungal agents—amphotericin B, fluconazole, flucytosine, itraconazole, posaconazole, and voriconazole—were tested. The patients’ demographic data and clinical information were abstracted for further analyses. Antifungal regimens consisting of amphotericin B with or without fluconazole or flucytosine were administered for induction treatment of these patients, followed with intravenous or oral fluconazole for maintenance therapy. Clinical outcomes were defined by 14- and 30-day mortality rates. Risk factors associated with outcomes were fitted in a logistic regression model by univariate or multivariate method. Eighty-five patients with C. neoformans var. grubii fungemia were enrolled in the study. The Sequential Organ Failure Assessment Score, Glasgow Coma Scale, Charlson comorbidity score, and adequate duration of therapy for amphotericin B were predictors for mortality in univariate analysis. Antifungal susceptibility testing with YeastONE™ does not predict clinical outcomes of C. neoformans var. grubii fungemia. Greater disease severity, high comorbidities, poor consciousness level, and inappropriate treatment were associated with increased mortality in cryptococcemia cases. Cryptococcus neoformans is an encapsulated yeast living in both plants and animals that is composed of three main serotypes: C. neoformans var. grubii, C. neoformans var. gattii, and C. neoformans var. neoformans. C. neoformans var. grubii is the most common disease-causing Cryptococcus species worldwide. C. neoformans var. gattii is more prevalent than C. neoformans var. neoformans in both tropical and subtropical regions of Asia. C. neoformans causes severe, even fatal, diseases such as pulmonary infection, bloodstream infection, skin and soft tissue infection, bone and joint infection, central nervous system infection, and disseminated infection, regardless of host immunocompetence. We conducted a retrospective study on 85 patients who contracted cryptococcemia from January 1, 2009, to December 31, 2016. This work conducted both microbiological and clinical studies involving in vitro susceptibility testing, demographic data, comorbidities, treatment modalities, and treatment outcomes. We utilized a modern medical technique-based instrument, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS; Biotyper, Bruker Daltonics, Inc.), which determines the unique proteomic fingerprint of an organism, to identify the C. neoformans serotype. We utilized Thermo Fisher Scientific™ Sensititre™ YeastONE™ colorimetric broth microdilution plates coupled with a Vizion™ Digital MIC Viewing System (a computer-assisted optical reading machine) to determine the in vitro susceptibility of amphotericin B, flucytosine, fluconazole, itraconazole, posaconazole, and voriconazole against 85 C. neoformans var. grubii blood isolates. In conclusion, the susceptibility patterns of these antifungal agents did not correlate significantly with treatment outcomes. However, a lower disease severity score, a lower Glasgow Coma Scale score, fewer comorbidities, and adequate amphotericin B treatment duration were predictors for treatment success in univariate analysis.

The relation between antifungal susceptibility and treatment outcomes is not well-characterized. There is paucity of surveillance data for cerebrospinal fluid (CSF) isolates of cryptococcus investigated with YEASTONE colorimetric broth microdilution susceptibility testing. A retrospective study of laboratory-confirmed cryptococcus meningitis (CM) patients was conducted. The antifungal susceptibility of CSF isolates was determined using YEASTONE colorimetric broth microdilution. Clinical parameters, CSF laboratory indices, and antifungal susceptibility results were analyzed to identify risk factors for mortality. High rates of resistance to fluconazole and flucytosine were observed in this cohort. Voriconazole had the lowest MIC (0.06 µg/mL) and lowest rate of resistance (3.8%). In a univariate analysis, hematological malignancy, concurrent cryptococcemia, high Sequential Organ Failure Assessment (SOFA) score, low Glasgow coma scale (GCS) score, low CSF glucose level, high CSF cryptococcal antigen titer, and high serum cryptococcal antigen burden were associated with mortality. In a multivariate analysis, meningitis with concurrent cryptococcemia, GCS score, and high CSF cryptococcus burden, were independent predictors of poor prognosis. Both early and late mortality rates were not significantly different between CM wild type and non-wild type species.

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). 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. 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. 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.

The durability of anti-SARS-CoV-2 antibodies after vaccination or infection varies among individuals, and the role of biological aging remains unclear. This study investigated the impact of PhenoAge acceleration on antibody responses and the risk of breakthrough infection. We analyzed serum concentration of antibodies against the receptor-binding domain of the SARS-CoV-2 S protein and calculated PhenoAge/PhenoAgeAccel using nine clinical biomarkers in 93 participants, including COVID-19-infected and vaccinated individuals, with follow-up every 3 months. Receiving ≥ 3 vaccine doses was associated with high antibody levels (OR: 4.36, p = 0.001), but natural infection was the strongest predictor (OR: 124.79, p < 0.001). Antibody titers > 2500 IU/mL protected against breakthrough infection (HR: 0.04, p = 0.0368). Despite ≥ 3 vaccine doses, individuals with titers ≤ 2500 IU/mL had increased risk (HR: 34.25, p = 0.0155). PhenoAge acceleration was associated with higher infection risk (HR: 4.75, p = 0.042). Booster vaccination and natural infection are key to sustaining high antibody levels. Accelerated biological aging may increase infection risk. High antibody levels are essential to prevent breakthrough SARS-CoV-2 infection, and vaccine doses alone are insufficient without an adequate antibody response.