Therapeutic Advances in Infectious Disease最新文献

Background: Infection prevention and control (IPC) measures during the coronavirus disease 2019 (COVID-19) pandemic have led to a reduction in respiratory viral infections. However, these infections showed a resurgence in the post-COVID-19 era. Respiratory viral infections often exacerbate respiratory diseases.

Objectives: This study aimed to determine how the relaxation of IPC measures affects the incidence of virus-related acute exacerbations in various respiratory diseases.

Design: A retrospective study conducted at a tertiary care facility.

Methods: This study retrospectively assessed data from adult patients aged 18 years and older who visited the emergency department (ED) of a tertiary medical centre in Kobe, Japan, from 1 October 2020 to 12 March 2024. We identified patients who visited because of chronic obstructive pulmonary disease (COPD) exacerbation, asthma exacerbation or acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) and classified them into two groups based on the pre-relaxation and post-relaxation of IPC measures. The detection rates and respiratory viruses identified using multiplex polymerase chain reaction were compared between the groups.

Results: The total number of ED visits was 84,183 involving 129 cases of COPD exacerbation, 156 cases of asthma exacerbation and 68 cases of AE-IPF. Virus-related COPD exacerbations were significantly more frequent after the relaxation of IPC measures than before (7.7% vs 52.5%, p < 0.001). Similarly, virus-related asthma exacerbations occurred significantly more frequently after relaxation than before (39.7% vs 66.7%, p = 0.009). In contrast, no significant difference in the virus-associated AE-IPF was observed before and after relaxation (2.5% vs 5.0%, p = 0.61).

Conclusion: Relaxation of IPC measures may increase virus-related exacerbations in COPD and asthma.

New human immunodeficiency virus (HIV) cases related to injection drug use (IDU) in the United States increased between 2016 and 2022. The uptake of preexposure prophylaxis (PrEP) is exceedingly low in persons who inject drugs (PWID) despite its efficacy to prevent HIV. There are multilevel barriers in the PrEP care cascade for PWID. We need a combination of effective HIV prevention strategies, including PrEP, treatment for substance use disorder, and syringe services programs (SSP) to reverse the trend. A major challenge is the lack of knowledge and skills in harm reduction practices and addiction care in the infectious disease (ID) workforce. ID clinicians could benefit from education in harm reduction and addiction, including taking on the responsibility of prescribing buprenorphine or navigating the resources for it. Addiction clinicians could benefit from education on PrEP and related program implementation knowledge. Both specialties need to comprehensively evaluate and address the risks for HIV acquisition in PWID. We should create integrated clinical programs between ID and addiction. We should improve HIV screening for hospitalized PWID. We should expand low-barrier integrated clinics with flexible hours, walk-in appointments, same-day PrEP starts, and collocated laboratory and pharmacy services. Other entities that could provide integrated care include substance detoxification and rehabilitation programs, SSPs, opioid treatment programs (OTP), community pharmacies, and mobile health clinics. Long-acting injectable PrEP for PWID is an attractive option for HIV prevention, but robust implementation programs are necessary for roll-out. We still need to address upstream barriers to care for PWID, including stigma and health disparities. We need to continue to advocate for policy changes and funding for SSPs and OTPs to provide comprehensive HIV prevention.

Background: People who use drugs (PWUD) are at increased risk for severe infections and face many barriers when completing conventional, typically parenteral antimicrobial treatments. Despite evidence supporting various antibiotic options, such as oral antibiotic therapy, there has been limited uptake of these strategies by many clinicians.

Objectives: Create a training for hospital-based clinicians detailing harm reduction and various antimicrobial treatment options for the care of PWUD with severe infections. Examine current hospital-based clinician practices regarding the care of PWUD. Compare pre- and post-training clinician knowledge and comfort around various antibiotic treatment options, harm reduction, and substance use stigma.

Design: The study design was a pre- and post-intervention descriptive survey. The intervention was the training session. Surveys were completed by participants before and after the training. Surveys were completed by participants before and after the training and asked about participants' practices and attitudes regarding PWUD and treatment options.

Methods: The training was provided to hospital-based clinicians across eight different sites in four different states from November 2022 to November 2023. We examined knowledge, attitudes, and practices around treating injection drug use-associated infections, patients with substance use disorders, and comfort with antimicrobial treatment options using pre-and post-training surveys. We also used a modified version of a validated substance use stigma instrument to measure stigma pre- and post-training. For paired pre-post survey data, we used McNemar's test to compare Likert scale responses.

Results: Of 167 study participants, 126 (75%) completed the pretraining survey, and 42 (25%) provided paired pre-post survey responses. Among the 126 pre-survey respondents, 64 (51%) were trainees, 75 (60%) frequently treated patients with injection drug use-associated infections, and 61 (50%) reported consistently applying harm reduction strategies to these patients in the hospital. Post-training, participants with paired data were significantly more likely to agree with applying harm reduction principles to the care of PWUD (pre, 23 (55%); post, 39 (95); p < 0.001) and discussing safer drug use practices (pre, 16 (38%); post, 29 (69%); p = 0.004).

Conclusion: Our study shows that an interactive training for hospital-based clinicians can significantly improve clinician knowledge and comfort with applying harm reduction strategies and with offering various antibiotic treatment options to PWUD with severe infections.

Background: Carbapenem-resistant Enterobacterales (CRE) are a significant public health threat affecting human health globally. Unfortunately, the incidence of CRE has increased globally, raising the red flag for the need for an urgent plan for this serious and worrisome problem.

Objectives: We aimed to identify the prevalence and genetic characterization of CRE in addition to determining antibiotic resistance profiles and the effect of independent variables on carbapenemase gene types.

Design: The study is a retrospective cross-sectional study conducted at a tertiary care hospital in East Jerusalem.

Methods: Data were collected from microbiology, molecular, and infectious diseases units from May 2019 till November 2023. Non-repetitive isolates that tested positive for CRE according to the CLSI (M100, S29, 2023) and American Society for Microbiology Diagnostic Microbiology Proceedings manual were included with no age exclusion.

Results: A total of 599 CRE non-repetitive isolates were included, carbapenemase detected (C-CRE detected) genes were seen in 421 isolates, while the remaining 178 isolates were carbapenemase not detected (C-CRE not detected). The most common carbapenemase gene was bla NDM (347 isolates, 82.4%), followed by bla OXA-48 (55 isolates, 13.1%). The prevalence of CRE from total cultures (gram-negative, gram-positive, and no growth) during the study period was 2.4%, while the prevalence of CRE from Enterobacterales was 20.6%. The prevalence of CRE increased over the study years with a notable increase between 2020 and 2021, Klebsiella species were the most common carbapenem-resistant bacterial genera, while surveillance anal swab culture was the most dominant culture site from where CRE isolates were isolated. Antibiotic resistance varied according to carbapenemase gene type and bacterial genera.

Conclusion: CRE is a growing problematic health issue that spotlights the urgent need for integrated, complete, and appropriate national antimicrobial stewardship and infection prevention and control programs.

Background: Immunosuppressive treatment can attenuate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced immune responses. Moreover, SARS-CoV-2 has neuroinvasive potential and may induce a persistent pro-inflammatory milieu following infection.

Objectives: To investigate if diminished post-vaccine humoral responses can be overcome with additional vaccine doses and/or breakthrough COVID-19 infections, and if COVID-19 infection can lead to a pro-inflammatory state with neuroaxonal/neuroglial injury in the intermediate-term in patients with central nervous system (CNS) neuroimmunological diseases.

Design: A prospective observational study conducted at National Neuroscience Institute, Singapore.

Methods: Serum levels of SARS-CoV-2 neutralising antibodies (NAbs) were measured in patients with CNS neuroimmunological diseases following their fourth SARS-CoV-2 mRNA vaccine (V4), or after breakthrough COVID-19 infection following three prior SARS-CoV-2 mRNA vaccinations, or both. Serum levels of pro-inflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor (TNF) were evaluated post-COVID-19 infection and post-V4, compared to baseline within individuals. Serum neurofilament-light chain (NfL) and glial fibrillary acidic protein (GFAP), biomarkers of neuroaxonal and astroglial injury, respectively, were measured at baseline and post-COVID-19 infection within patients with relapsing-remitting multiple sclerosis (RRMS) and neuromyelitis optica spectrum disorder (NMOSD).

Results: Sixty-one patients with various CNS neuroimmunological diseases were recruited, including 34 with MS and 19 with NMOSD. All had received at least three doses of the SARS-CoV-2 mRNA vaccine. Patients on anti-CD20/sphingosine-1-phosphate-receptor modulators (S1PRM) showed significantly reduced NAbs levels in both post-V4 and post-COVID-19 infection scenarios, compared to patients on other immunotherapies. No significant differences between baseline and post-COVID-19 infection concentrations of IL-6 and TNF were observed. Within RRMS and NMOSD patients, NfL and GFAP levels remained similar between baseline and post-COVID-19 infection.

Conclusion: Anti-CD20/S1PRM treatments are associated with persistently diminished humoral responses post-V4/infection. Patients with CNS neuroimmunological diseases do not show biomarker evidence of intermediate-term pro-inflammatory states and neural injury after COVID-19 infection.

Background: Fascioliasis, caused by Fasciola hepatica and F. gigantica, is a neglected tropical disease that has significant medical and veterinary importance. This foodborne zoonotic trematodiases primarily affects poor rural populations in tropical and subtropical areas, where prevalence can be as high as 21%.

Objective: This study aims to characterize the clinical features, laboratory findings, and outcomes of fascioliasis in a real-world cohort.

Design: Retrospective study.

Methods: Patients ⩾ 18 years old diagnosed with fascioliasis were identified from TriNetX, a global federated research network, on October 26, 2024. We used the International Classification of Diseases results to define fascioliasis (ICD-10 code B66.3) for the period 2021-2024. These data include demographics, diagnoses, comorbidities, procedures, clinical laboratory results, and medications. All variables except outcomes were not time-bound to the diagnosis date.

Results: In a cohort of 174 predominantly middle-aged, female, and Caucasian patients, we found high rates of essential hypertension, neoplasms, heart disease, liver disease, and sleep disorders. Key symptoms included upper abdominal pain, skin complaints, dyspnea, and malaise/fatigue. Some outcomes were hepatomegaly, cholelithiasis, and cholangitis in 10% of patients, with hepatic cirrhosis being rare. Among hospitalized patients within 3 months of diagnosis, 63% experienced abdominal pain. Of the 13 patients who developed cholangitis or cholelithiasis, most were men, had abdominal pain, nausea/vomiting, dysphagia, and ascites with a history of liver or intrahepatic bile neoplasia. A total of 90-day mortality was low (less than 6%). Triclabendazole was reported in only 6% of these patients.

Conclusion: In a large real-world case series of fascioliasis, we found a high frequency of comorbidities and typical gastrointestinal symptoms. The low use of triclabendazole may be due to limited access to the product in certain countries or its omission from the database if prescribed in the outpatient setting. Mortality was very low, but biliary and liver complications warrant characterization through additional prospective clinical studies.

Background: Tumor necrosis factor-alpha (TNF-α) is implicated in the pathogenesis of autoimmune conditions and sepsis. Although anti-TNF-α therapies have demonstrated clinical efficacy in rheumatoid arthritis (RA), there is no established evidence for benefit in patients with sepsis.

Objectives: We sought to quantify circulating TNF-α in patients with RA and compare results to TNF-α levels in sepsis.

Design: We performed a systematic review and meta-analysis of circulating TNF-α in patients with RA. We searched Cochrane Library, Google Scholar, Ovid Embase, Ovid MEDLINE, Scopus, and Web of Science Core Collection databases from inception until May 30, 2023. We included randomized controlled studies and observational reports containing more than ten subjects that reported mean serum or plasma TNF-α levels. We used the Newcastle-Ottawa Scale to assess methodological quality of studies.

Data sources and methods: Summary data were extracted and analyzed using a random-effects model to estimate the pooled mean circulating TNF-α. Circulating TNF-α in RA was compared to TNF-α levels reported in our systematic review and meta-analysis characterizing cytokine levels in sepsis.

Results: We identified and screened 8764 studies, and 104 studies satisfied the inclusion criteria (5399 total participants, including 4419 females). Pooled estimated mean RA TNF-α was 23.1 pg/mL (95% CI 17.8-30.1) in the random-effects model. There was significantly lower TNF-α in RA patients using disease-modifying antirheumatic drugs (DMARDs, p = 0.04) and patients using corticosteroids (p = 0.01). After adjustment for age and sex, there was no significant difference between TNF-α in RA compared to sepsis.

Conclusion: No significant difference between adjusted TNF-α levels in patients with RA versus sepsis was determined. Since TNF-α antagonists show benefit in RA but not sepsis despite comparable circulating concentrations, we conclude TNF-α does not contribute to sepsis pathogenesis. TNF-α concentration may be slightly higher due to study heterogeneity.

Trial registration: This investigation was registered in PROSPERO (CRD42023425361).

A 79-year-old female diagnosed with myelodysplastic syndrome (MDS) and germline GATA2 mutation, on compassionate cobimetinib, was admitted with subacute cough and dyspnea. Chest imaging demonstrated a new, large, left hilar mass and consolidation with scattered diffuse mediastinal, supraclavicular, and hilar lymphadenopathy. A core biopsy of the right supraclavicular lymph node was performed. Acid-fast bacilli (AFB) cultures from both the lymph node and blood were positive, while all fungal cultures were negative. Two distinct AFB colonies were observed on solid media and identified as Mycobacterium avium complex and Mycobacterium kansasii. Disseminated non-tuberculous mycobacterial infections involving two distinct species are rare, pose treatment challenges, and may correlate with cobimetinib administration for MDS, as well as GATA2 germline mutations.