Infection最新文献

Next-generation sequencing (NGS) has revolutionized clinical microbiology, particularly in diagnosing respiratory infectious diseases and conducting epidemiological investigations. This narrative review summarizes conventional methods for routine respiratory infection diagnosis, including culture, smear microscopy, immunological assays, image techniques as well as polymerase chain reaction(PCR). In contrast to conventional methods, there is a new detection technology, sequencing technology, and here we mainly focus on the next-generation sequencing NGS, especially metagenomic NGS(mNGS). NGS offers significant advantages over traditional methods. Firstly, mNGS eliminates assumptions about pathogens, leading to faster and more accurate results, thus reducing diagnostic time. Secondly, it allows unbiased identification of known and novel pathogens, offering broad-spectrum coverage. Thirdly, mNGS not only identifies pathogens but also characterizes microbiomes, analyzes human host responses, and detects resistance genes and virulence factors. It can complement targeted sequencing for bacterial and fungal classification. Unlike traditional methods affected by antibiotics, mNGS is less influenced due to the extended survival of pathogen DNA in plasma, broadening its applicability. However, barriers to full integration into clinical practice persist, primarily due to cost constraints and limitations in sensitivity and turnaround time. Despite these challenges, ongoing advancements aim to improve cost-effectiveness and efficiency, making NGS a cornerstone technology for global respiratory infection diagnosis.

Purpose: This study investigates the care provision and the role of infectious disease (ID) specialists during the coronavirus disease-2019 (COVID-19) pandemic.

Methods: A survey was conducted at German study sites participating in the Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS). Hospitals certified by the German Society of Infectious diseases (DGI) were identified as ID centers. We compared care provision and the involvement of ID specialists between ID and non-ID hospitals. Then we applied a multivariable regression model to analyse how clinical ID care influenced the mortality of COVID-19 patients in the LEOSS cohort.

Results: Of the 40 participating hospitals in the study, 35% (14/40) were identified as ID centers. Among those, clinical ID care structures were more commonly established, and ID specialists were always involved in pandemic management and the care of COVID-19 patients. Overall, 68% (27/40) of the hospitals involved ID specialists in the crisis management team, 78% (31/40) in normal inpatient care, and 80% (28/35) in intensive care. Multivariable analysis revealed that COVID-19 patients in ID centers had a lower mortality risk compared to those in non-ID centers (odds ratio: 0.61 (95% CI 0.40-0.93), p = 0.021).

Conclusion: ID specialists played a crucial role in pandemic management and inpatient care.

Purpose: Recently, cases of serious illness in newborns infected with Echovirus 11 have been reported in Europe, including Italy. Here, we report the case of a newborn diagnosed with disseminated Echovirus 11 infection, which occurred in October 2023 in the Province of Bolzano, Italy.

Methods: A molecular screening, by Real-Time RT-PCR, was employed to analyse the cerebrospinal fluid, blood and stool samples, and nasal swabs. The entire viral genome was sequenced using both Illumina and Nanopore technologies.

Results: The patient was admitted to hospital due to fever. Molecular testing revealed the presence of enterovirus RNA. Typing confirmed the presence of Echovirus 11. The patient was initially treated with antibiotic therapy and, following the diagnosis of enterovirus infection, also with human immunoglobulins. Over the following days, the patient remained afebrile, with decreasing inflammation indices and in excellent general condition. Genomic and phylogenetic characterization suggested that the strain was similar to strains from severe cases reported in Europe.

Conclusions: Despite the low overall risk for the neonatal population in Europe, recent cases of Echovirus 11 have highlighted the importance of surveillance and complete genome sequencing is fundamental to understanding the phylogenetic relationships of Echovirus 11 variants.

Common pathways may underlie the association between COVID-19 and risk for Alzheimer's disease (AD). We conjecture that severe COVID-19 may contribute to AD onset in predisposed individuals through aberrant MDSCs expression and increased IL-6 expression levels leading to immunosuppression in inflamed brains. Research studies are needed to gain empirical evidence to strengthen the hypothesis of the involvement of MDSCs and IL-6 in the formation of AD following COVID-19 infection and possibly vaccination enabling a more in-depth understanding of the role of immunosuppression in the onset of neurodegenerative diseases at any age. Identifying why those who get severe COVID-19 are more likely to develop AD may offer a novel therapeutic approach to delay or prevent cognitive decline.

Purpose: We aimed to explore the prevalence and within-host evolution of resistance in polymyxin-heteroresistant carbapenem-resistant Klebsiella pneumoniae (PHR-CRKP) in critically ill patients.

Methods: We performed an epidemiological analysis of consecutive patients with PHR-CRKP from clinical cases. Our study investigated the within-host resistance evolution and its clinical significance during polymyxin exposure. Furthermore, we explored the mechanisms underlying the dynamic evolution of polymyxin resistance at both subpopulation and genetic levels, involved population analysis profile test, time-killing assays, competition experiments, and sanger sequencing. Additionally, comparative genomic analysis was performed on 713 carbapenemase-producing K. pneumoniae strains.

Results: We enrolled 109 consecutive patients, and PHR-CRKP was found in 69.7% of patients without previous polymyxin exposure. 38.1% of PHR-CRKP isolates exhibited polymyxin resistance and led to therapeutic failure in critically ill scenarios. An increased frequency of resistant subpopulations was detected during PHR-CRKP evolution, with rapid regrowth of resistant subpopulations under high polymyxin concentrations, and a fitness cost in an antibiotic-free environment. Mechanistic analysis revealed that diverse mgrB insertions and pmrB hypermutations contributed to the dynamic changes in polymyxin susceptibility in dominant resistant subpopulations during PHR evolution, which were validated by comparative genomic analysis. Several deleterious mutations (e.g. pmrB^Leu82Arg, pmrB^Ser85Arg) were firstly detected during PHR-CRKP evolution. Indeed, specific sequence types of K. pneumoniae demonstrated unique deletions and deleterious mutations.

Conclusions: Our study emphasizes the high prevalence of pre-existing heteroresistance in CRKP, which can lead to polymyxin resistance and fatal outcomes. Hence, it is essential to continuously monitor and observe the treatment response to polymyxins in appropriate critically ill scenarios.

Background: Acute hepatitis E infection (HEV), with its high incidence in Europe, should be considered as a differential diagnosis of acute viral hepatitis and can in some cases manifest with pronounced neurological symptoms.

Clinical case: We report on a 33-year-old female patient with severe arthralgia, myalgia, headache and psychomotor deterioration. Laboratory analyses showed elevated transaminases without signs of cholestasis. Acute hepatitis E virus infection was detected in serum. She reported fatigue and dysesthesias not responsive to analgesics. Cerebrospinal fluid (CSF) analysis revealed an inflammatory syndrome. HEV RNA was detected in the CSF. The infection remained mild, but dysesthesias persisted. Eight weeks after the first admission, the symptoms worsened again. Complete and sustained remission was achieved following intravenous corticosteroid treatment.

Conclusion: In patients with acute neurological symptoms and liver enzyme elevation, HEV infection should be considered. Neurologic symptoms such as fatigue, arthralgia, myalgia and dysesthesia along with psychomotor retardation should prompt CSF analysis.

Purpose: Tumor necrosis factor inhibitors (TNFi) are known to increase the risk of tuberculosis (TB) reactivation, though cases involving Mycobacterium bovis are rarely reported.

Case presentation/results: We describe a case of disseminated TB with M. bovis in a 78-year-old woman with a negative Interferon-Gamma-Release Assay (IGRA), taking adalimumab due to rheumatoid polyarthritis, which resulted in a fatal outcome. The atypical clinical and histopathological features were initially interpreted as sarcoidosis. The case occurred in Switzerland, an officially bovine tuberculosis-free country. The whole genome sequence of the patient's cultured M. bovis isolate was identified as belonging to the animal lineage La1.2, the main genotype in continental Europe, but showed significant genetic distance from previously sequenced Swiss cattle strains. In a literature review, four cases of bovine tuberculosis reactivation under TNFi treatment were identified, with pulmonal, oral and intestinal manifestations. Similar to our patient, two cases presented a negative IGRA before TNFi initiation, which later converted to positive upon symptomatic presentation of M. bovis infection.

Conclusion: This case highlights the diagnostic challenges of TB in immunosuppressed patients, the limited sensitivity of IGRA, and the importance of considering TB reactivation even in regions declared free of bovine tuberculosis. Detailed patient histories, including potential exposure to unpasteurized dairy products, are essential for guiding preventive TB treatment before TNFi initiation.

In this image, the autors reinterprate "The Thinker" from Auguste Rodin to transfer knowledge about dengue fever, which can range from flu-like illness to severe hemorrhagic fever. By fostering awareness and understanding of dengue fever, we strive to empower individuals and communities in the ongoing fight against dengue and other infectious threats.

Purpose: This executive summary of a German national guideline aims to provide the most relevant evidence-based recommendations on the diagnosis and treatment of nosocomial pneumonia.

Methods: The guideline made use of a systematic assessment and decision process using evidence to decision framework (GRADE). Recommendations were consented by an interdisciplinary panel. Evidence analysis and interpretation was supported by the German innovation fund providing extensive literature searches and (meta-) analyses by an independent methodologist. For this executive summary, selected key recommendations are presented including the quality of evidence and rationale for the level of recommendation.

Results: The original guideline contains 26 recommendations for the diagnosis and treatment of adults with nosocomial pneumonia, thirteen of which are based on systematic review and/or meta-analysis, while the other 13 represent consensus expert opinion. For this key summary, we present 11 most relevant for everyday clinical practice key recommendations with evidence overview and rationale, of which two are expert consensus and 9 evidence-based (4 strong, 5 weak and 2 open recommendations). For the management of nosocomial pneumonia patients should be divided in those with and without risk factors for multidrug-resistant pathogens and/or Pseudomonas aeruginosa. Bacterial multiplex-polymerase chain reaction (PCR) should not be used routinely. Bronchoscopic diagnosis is not considered superior to´non-bronchoscopic sampling in terms of main outcomes. Only patients with septic shock and the presence of an additional risk factor for multidrug-resistant pathogens (MDRP) should receive empiric combination therapy. In clinically stabilized patients, antibiotic therapy should be de-escalated and focused. In critically ill patients, prolonged application of suitable beta-lactam antibiotics should be preferred. Therapy duration is suggested for 7-8 days. Procalcitonin (PCT) based algorithm might be used to shorten the duration of antibiotic treatment. Patients on the intensive care unit (ICU) are at risk for invasive pulmonary aspergillosis (IPA). Diagnostics for Aspergillus should be performed with an antigen test from bronchial lavage fluid.

Conclusion: The current guideline focuses on German epidemiology and standards of care. It should be a guide for the current treatment and management of nosocomial pneumonia in Germany.

Purpose: Sepsis causes significant worldwide morbidity and mortality. Inability to clear an infection and secondary infections are known complications in severe sepsis and likely result in worsened outcomes. We sought to characterize risk factors of these complications.

Methods: We performed a secondary analysis of clinical data from 401 subjects enrolled in the PHENOtyping sepsis-induced Multiple organ failure Study. We examined factors associated with prolonged infection, defined as infection that continued to be identified 7 days or more from initial identification, and secondary infection, defined as new infections identified ≥ 3 days from presentation. Multivariable adjustment was performed to examine laboratory markers of immune depression, with immunocompromised and immunocompetent subjects analyzed separately.

Results: Illness severity, immunocompromised status, invasive procedures, and site of infection were associated with secondary infection and/or prolonged infection. Persistent lymphopenia, defined as an absolute lymphocyte count (ALC) < 1000 cells/µL twice in the first five days, and persistent neutropenia, defined as absolute neutrophil count (ANC) < 1000 cells/µL twice in the first five days, were associated with secondary and prolonged infections. When adjusted in multivariable analysis, persistent lymphopenia remained associated with secondary infection in both immunocompromised (aOR = 14.19, 95% CI [2.69, 262.22] and immunocompetent subjects (aOR = 2.09, 95% CI [1.03, 4.17]). Persistent neutropenia was independently associated with secondary infection in immunocompromised subjects (aOR = 5.34, 95% CI [1.92, 15.84]). Secondary and prolonged infections were associated with worse outcomes, including death.

Conclusions: Laboratory markers of immune suppression can be used to predict secondary infection. Lymphopenia is an independent risk factor in immunocompromised and immunocompetent patients for secondary infection.