Journal of Microbiology Immunology and Infection最新文献

Background: Respiratory syncytial virus (RSV) is a leading cause of respiratory infections in infants and young children. The COVID-19 pandemic significantly disrupted global RSV epidemiology. This study aimed to investigate the impact of the pandemic on RSV epidemiology in northern Taiwan from 2018 to 2023.

Methods: We retrospectively enrolled children aged <5 years with positive RSV antigen tests from 2018 to 2023, dividing into four study periods based on the COVID-19 pandemic timeline: 2018-2019, 2020-2021, 2022, 2023.

Results: The number of RSV positive cases was 1155 in 2018-2019, 780 in 2020-2021, 784 in 2022, and 1116 in 2023. The proportion of RSV-positive children aged 2-5 years increased progressively from 23.9 % (2018-2019) to 52.0 % (2023) (P < 0.001). The mean age of infected children increased over time (P < 0.001). Among children under 2 years old, hospitalization rates declined from 82.0 % (2018-2019) to 68.1 % (2023) in subsequent intervals (P < 0.001). Compared to 2018-2019, seasonal peaks delayed by 2 months in 2020, absent in 2021, and delayed by 3 and 2 months in 2022 and 2023, respectively. The RSV seasonal peaks varied with shortened peaks during the COVID pandemic. ICU admission rates declined from 2.9 % to 1.9 % while mortality declined from 0.2 % to 0 %. Independent risk factors for severe disease included age under 3 months, bronchopulmonary dysplasia, congenital heart disease, cerebral palsy, neurodevelopmental disorders, and co-infection with Streptococcus pneumoniae.

Conclusions: The COVID-19 pandemic significantly altered the seasonality and clinical characteristics of RSV infections in northern Taiwan, likely due to the varying intensity of public health interventions.

Objectives: Vancomycin-resistant enterococcal bloodstream infections (VRE-BSIs) carry high mortality in patients with malignancy. While neutropenia is a known risk factor for mortality in patients with malignancy and BSI, its impact on the effectiveness of daptomycin and linezolid in VRE-BSI is not well defined.

Methods: We conducted a multicenter cohort study of hospitalized patients aged ≥18 years with malignancy and VRE-BSI between 2010 and 2021. Eligible patients received linezolid or high-dose daptomycin (≥8 mg/kg). Those with pneumonia or Enterococcus species other than E. faecium were excluded. Only the first VRE-BSI episode per patient was analyzed. The primary outcome was 14-day mortality, assessed using multivariable logistic regression.

Results: A total of 474 patients were included (linezolid, n = 90; daptomycin, n = 384); 128 (27.0 %) had neutropenia. The 14-day mortality was 32.9 % (156/474). Mortality was higher in neutropenic than non-neutropenic patients (45/128 [35.2 %] vs. 111/346 [32.1 %]; P = 0.005). Among neutropenic patients, mortality was 6/8 (75.0 %) with linezolid and 49/120 (40.8 %) with daptomycin; in non-neutropenic patients, mortality was 16/82 (19.5 %) and 85/264 (32.2 %), respectively. In multivariable analysis, linezolid use in neutropenic patients was associated with higher mortality (aOR 8.48; 95 % CI, 1.40-51.30; P = 0.02).

Conclusions: Neutropenia was associated with worse outcomes in patients with VRE-BSI, and linezolid-treated neutropenic patients showed higher mortality in this cohort. These findings should be interpreted cautiously given the small sample size and residual confounding. High-dose daptomycin may be considered, particularly in neutropenic patients, but confirmatory studies are needed.

Background: Interferon-gamma release assays (IGRAs) measure immune responses to pathogen-specific antigens such as tuberculosis. However, the assay hinges on a functional immune system. Whether IGRAs can be used to identify heart transplant candidates with impaired immunity and worse prognosis is not known.

Methods: From August 1st^, 2014 to August 31st^, 2018, all heart transplant candidates at a medical center in Taiwan who received an IGRA (QuantiFERON®-TB Gold In-Tube) during transplant evaluation to screen for latent tuberculosis infection were included. Inadequate immunity was defined as a response of <1 IU/ml of interferon-γ (IFN-γ) to the common mitogen in the positive control tube of the IGRA. Patients were followed until death or January 31st, 2019 for all-cause mortality and subsequent infections.

Results: A total of 103 patients were included, and 23 (22.3 %) had inadequate mitogen responses. After a median follow-up duration of 676 days (interquartile range [IQR] 387-1299), 34 (33.0 %) patients received a heart transplant and 23 (22.3 %) patients died. Forty-eight (46.6 %) patients developed infections, predominantly bacteremia (37.5 %). Those with inadequate mitogen responses had significantly higher rates of mortality (39.1 % vs. 17.5 %, p = 0.028) and infections (65.2 % vs. 41.3 %, p = 0.042). In the multivariate analysis, inadequate responses to mitogen were significantly associated with mortality and infections (hazard ratio [HR] 3.36, confidence interval [CI] 1.22-9.23, p = 0.019; HR 2.75, CI 1.18-6.40, p = 0.019).

Conclusions: Patients with heart failure and inadequate mitogen responses by IGRAs had a higher risk of mortality and infection. IGRAs may have a novel application in prognostication of heart transplant candidates.

Background: To compare diagnostic performances and accuracy of non-invasive specimens and bronchoalveolar lavage fluid (BALF) for diagnosing Pneumocystis pneumonia (PCP) in immunocompromised pneumonia patients.

Methods: A prospective study of 112 immunocompromised patients to evaluate P. jirovecii fungal loads in paired sputum and BALF from the same patients. Patients were classified as definite PCP, probable PCP, and non-PCP based on criteria blinded to qPCR results. Optimal diagnostic cut-offs were derived, and agreement between specimen types was analyzed.

Results: A BALF fungal load threshold of 2,613 DNA copies/μL demonstrated high sensitivity (82.6 %, 95 % CI: 62.9-93.0) and specificity (96.7 %, 95 % CI: 90.8-99.1) for PCP diagnosis. In sputum, a cut-off of 474 DNA copies/μL offered moderate sensitivity (65.2 %, 95 % CI: 44.9-81.2) and high specificity (89.0 %, 95 % CI: 80.9-93.9), enabling the exclusion of PCP in patients with low clinical suspicion. Fungal loads in sputum correlated well with BALF but showed greater variability in confirmed PCP cases, highlighting limitations for non-invasive diagnosis in high-risk patients.

Conclusion: Non-invasive fungal load in sputum provides a valuable tool for excluding PCP in immunocompromised pneumonia patients, potentially reducing the need for bronchoscopy.

Background: To disclose Proteus mirabilis copper detoxification mechanisms, we performed Tn5-mutagenesis and an hha gene-disrupted mutant was isolated, exhibiting increased copper sensitivity. We investigated the role of Hha in P. mirabilis, focusing on the virulence aspects.

Methods: Assays of copper susceptibility, swarming/swimming, biofilm formation, persister cell formation, killing by macrophages, adhesion, invasion, urothelial cell cytokine expression, wax moth virulence, were performed. The invertible element assay, TEM, EMSA and SDM were used to examine MR/P fimbria expression, flagellar production, Hha-flhDC promoter binding and the importance of Hha 13th amino acid cysteine (Hha C13), respectively. RT-PCR was conducted to demonstrate the tomB-hha operon. Hha-related gene expression and regulation were elucidated by RT-qPCR and transcriptional reporter assay.

Results: We showed P. mirabilis hha and tomB form an operon and TomB antagonized Hha toxicity. The Hha was involved in copper susceptibility, swimming/swarming, biofilm formation and persister cell formation. The hha mutant had lower adhesion/invasion abilities, triggered higher cytokine expression of urothelial cells and was more sensitive to macrophage killing and attenuated in wax moth. P. mirabilis Hha C13 is crucial in toxicity and Hha-TomB interaction. Deletion of hha reduced relA/rpoS expression. CpxR controlled hha promoter activity. Finally, copper was the signal to induce cpxR/hha expression.

Conclusion: We disclosed that P. mirabilis Hha of the toxin-antitoxin system (TA) participates in virulence and its regulation by copper-sensing CpxR. This work provides Hha as a potential drug target for combating P. mirabilis urinary tract infections and opens new perspectives for studying TA aiming at controlling bacterial virulence.

Background: Multidrug-resistant Klebsiella pneumoniae (MDR-KP) leads global health concerns as an infectious agent due to many virulence factors, including biofilm formation. The growing urgency for alternative treatment strategies beyond antibiotics has renewed interest in bacteriophages. Pathogen evolution is dynamic and can lead to phage resistance.

Methods: Bacteriophages were isolated from environmental sources and screened against a panel of 280 MDR- K. pneumoniae clinical isolates (74 from 2018 to 2020 and 167 from 2022-23 and 39 environmental KP isolates). Phages were grouped by host range and DNA fingerprinting. Five candidate phages with unique and broad host coverage were selected for further characterization and genome sequencing.

Results: Five candidate phages exhibited diverse host range patterns, strong bacteriolytic activity and significant antibiofilm activity even at low multiplicity of infection. Whole genome sequencing analysis revealed phage KPØ6 to be a novel Taipevirus species with low intergenomic similarity to known phages, and it showed the broadest host range on isolates from the 2018-2020 panel. A significant rise in phage resistance among MDR-KP isolate panels of 2018-2020 and 2022-2023 was observed.

Conclusion: Lytic bacteriophages offer a promising alternative for tackling MDR-KP infections, especially within healthcare environments. The phages characterized in this study demonstrate strong potential for both biocontrol and therapeutic use against MDR-KP, including infections involving biofilms. However, the dynamic nature of bacterial evolution over five years reiterates the need to update phage banks.

Objectives: Diagnosing paediatric Community-Acquired Pneumonia (CAP) is challenging due to the difficulty in obtaining lung specimens. Studies suggest that the upper-airway density of Streptococcus pneumoniae is related to the risk and severity of CAP. We studied the association between S. pneumoniae and its density in the upper airways with CAP and its severity. Additionally, we examined the relationship between respiratory viral load and severe CAP.

Methods: Seven hundred fifteen children with radiologically confirmed CAP and 673 controls were enrolled over 11 years. Nasopharyngeal aspirates (NPA) were tested for 20 viruses and bacteria using semi-quantitative polymerase chain reaction (PCR). NPAs positive for S. pneumoniae were further analysed by quantitative PCR. Adjusted odds ratios (aORs) and 95 % confidence intervals (CIs) were calculated to assess the association between S. pneumoniae density and CAP and CAP severity.

Results: Fewer cases than controls were colonised with S. pneumoniae (culture: 37.6 % vs 51.9 %, p < .001; PCR: 55.3 % vs 69.1 %, p < .001), and the median density was lower (6.20 log¹⁰ copies/mL vs 6.62 log¹⁰ copies/mL, p < .001). No association was found between S. pneumoniae density and CAP severity. CAP severity was significantly associated with high Respiratory Syncytial Virus (RSV) load (aOR 2.26, 95 % CI 1.43-3.57, p < .001) or high Human Metapneumovirus (HMPV) load (aOR 4.32, 95 % CI 2.19-8.48, p < .001), adjusted by pneumococcal density, other pathogens, age, sex, comorbidities, prior antibiotics and season.

Conclusions: Detection and density of S. pneumoniae in the upper airways do not correlate with CAP presence or severity. High RSV and HMPV loads were linked to severe CAP.

Background: Acinetobacter seifertii, a recently identified member of the Acinetobacter calcoaceticus-Acinetobacter baumannii (Acb) complex, has emerged as a cause of severe human infections. It is closely related to Acinetobacter nosocomialis, a major pathogen of the Acb complex. Here, we aimed to explore the clinical and molecular differences between these two species.

Methods: This retrospective study enrolled 83 adults with A. seifertii bacteremia and 402 adults with A. nosocomialis bacteremia from four medical centers over a 9-year period. Species identification was confirmed using matrix-assisted laser desorption ionization-time of flight mass spectrometry and rpoB sequencing. Clinical information, antimicrobial susceptibility, and carbapenem resistance determinants were analyzed.

Results: There were no significant differences in the underlying diseases or mortality between patients with A. seifertii and A. nosocomialis bacteremia. However, A. seifertii bacteremia was more frequently associated with intensive care unit (ICU) admission, recent ICU stay, central venous catheter use, ventilator use at bacteremia onset, and pneumonia as the primary infection source than A. nosocomialis bacteremia. A. seifertii exhibited significantly lower susceptibility to colistin, amikacin, gentamicin, ceftazidime, and cefepime than A. nosocomialis. Carbapenem resistance was primarily mediated by ISAba1-bla_OXA-51-like in A. seifertii and IS1006-ΔISAba3-bla_OXA-58-like in A. nosocomialis.

Conclusion: A. seifertii and A. nosocomialis exhibit distinct antimicrobial susceptibility profiles and carbapenem resistance mechanisms but share similar mortality rates. The ability of both species to act as reservoirs of carbapenem resistance highlights the importance of accurate identification, antimicrobial stewardship, and infection control strategies to mitigate the spread of resistant strains.

Purpose: To evaluate the effectiveness and safety of oral levofloxacin verse trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of macrolides-resistant pertussis in pediatric outpatients.

Methods: A prospective observational study was conducted at a pediatric pertussis outpatient clinic during the pertussis outbreak in 2024. For eligible children with PCR-confirmed pertussis, administration of either levofloxacin (8-10 mg/kg/dose, once or twice daily) or TMP-SMX (4-20 mg/kg/dose, twice daily) depended on parents' preference. Effectiveness and safety were evaluated for the 5-14 days duration of levofloxacin and TMP-SMX treatment in terms of alleviation of cough symptoms, bacteriologic clearance of Bordetella pertussis and adverse effects.

Results: Among 193 enrolled pertussis cases, eighty-four (43.53 %) received levofloxacin and 109 (56.48 %) received TMP-SMX. After completing treatment, paroxysmal cough resolved or improved in 96.43 % of levofloxacin group and 94.50 % (103/109) of TMP-SMX group (p = 0.554). Nocturnal cough resolved or improved in 98.81 % of levofloxacin group and in 98.17 % of TMP-SMX group (p = 0.057). There was no significant difference in bacteriologic clearance rate between levofloxacin group and TMP-SMX group determined by PCR (92.00 % vs 87.06 %, p = 0.378) and culture (100 % vs 100 %, p > 0.378). Symptom resolution rate did not differ significantly among patients treated for 5 or 7 days with either levofloxacin or TMP-SMX. Adverse events were reported in 9.2 % of TMP-SMX-treated patients and 2.4 % of levofloxacin-treated patients (p < 0.05). Drug rash was reported in nine (8.26 %) TMP-SMX-treated patients.

Conclusions: Oral levofloxacin showed a comparable clinical effectiveness and a favorable safety profile to TMP-SMX for the treatment of non-severe pertussis with a 5-7 days course in children.

Background: Dialysis patients are vulnerable to SARS-CoV-2 infection and subsequent complications. However, the vaccine-induced immunity, especially against new variants, following two AZD1222 and two booster doses in hemodialysis patients remain largely unknown.

Methods: In this observational cohort study, we monitored immune responses in 127 hemodialysis patients receiving the 3^rd and 4th vaccinations until three months after the 4th immunization. Humoral and cellular immunity were assessed by anti-SARS-CoV-2 receptor-binding domain(RBD) antibody, neutralizing antibodies against the ancestral virus, delta, omicron BA.1 and BA.2 and SARS-CoV-2 specific IFN-γ releasing assay (Covi-FERON).

Results: The primary series and the fourth dose predominantly consisted of two-dose AZD1222 and mRNA-1273, respectively. The most common vaccines chosen for the third dose was mRNA-1273(n = 84), following by BNT 162b2(n = 38). Anti-RBD antibody increased to 13803.8 and 18197U/ml after the 3^rd and 4th vaccination, respectively, but dropped to 8709.6U/ml three months after the fourth vaccination. One month after the fourth vaccination, 99 %,98 %,51.5 % and 93.9 % participants had neutralizing antibodies against the ancestral virus, delta, omicron BA.1 and BA.2, respectively. 87.9 % and 81.8 % patients reacted to the ancestral or alpha and beta or gamma spike antigens in Covi-FERON, respectively, after four vaccinations. Higher Covi-FERON reactions were associated with increased IL-2 and IL-4 secretion. In linear mixed effect models, mRNA-1273 as the third vaccination was associated higher anti-RBD antibody titers and higher neutralization against the ancestral virus and delta compared with BNT162b2 but with higher mild adverse events following vaccination.

Conclusions: Two AZD1222 and two mRNA booster doses confer substantial humoral and cellular immunity against variants including omicron in hemodialysis patients.