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Antibiotics (Basel, Switzerland) Feb 2024The impact of bacterial pneumonia on patients with COVID-19 infection remains unclear. This prospective observational monocentric cohort study aims to determine the...
The impact of bacterial pneumonia on patients with COVID-19 infection remains unclear. This prospective observational monocentric cohort study aims to determine the incidence of bacterial community- and hospital-acquired pneumonia (CAP and HAP) and its effect on mortality in critically ill COVID-19 patients admitted to the intensive care unit (ICU) at University Hospital Olomouc between 1 November 2020 and 31 December 2022. The secondary objectives of this study include identifying the bacterial etiology of CAP and HAP and exploring the capabilities of diagnostic tools, with a focus on inflammatory biomarkers. Data were collected from the electronic information hospital system, encompassing biomarkers, microbiological findings, and daily visit records, and subsequently evaluated by ICU physicians and clinical microbiologists. Out of 171 patients suffering from critical COVID-19, 46 (27%) had CAP, while 78 (46%) developed HAP. Critically ill COVID-19 patients who experienced bacterial CAP and HAP exhibited higher mortality compared to COVID-19 patients without any bacterial infection, with rates of 38% and 56% versus 11%, respectively. In CAP, the most frequent causative agents were chlamydophila and mycoplasma; Enterobacterales, which were multidrug-resistant in 71% of cases; Gram-negative non-fermenting rods; and . Notably, no strains of were detected, and only a single strain each of and was isolated. The most frequent etiologic agents causing HAP were Enterobacterales and Gram-negative non-fermenting rods. Based on the presented results, commonly used biochemical markers demonstrated poor predictive and diagnostic accuracy. To confirm the diagnosis of bacterial CAP in our patient cohort, it was necessary to assess the initial values of inflammatory markers (particularly procalcitonin), consider clinical signs indicative of bacterial infection, and/or rely on positive microbiological findings. For HAP diagnostics, it was appropriate to conduct regular detailed clinical examinations (with a focus on evaluating respiratory functions) and closely monitor the dynamics of inflammatory markers (preferably Interleukin-6).
PubMed: 38391578
DOI: 10.3390/antibiotics13020192 -
Expert Review of Vaccines 2024Transmissible vaccines offer a novel approach to suppressing viruses in wildlife populations, with possible applications against viruses that infect humans as zoonoses -...
INTRODUCTION
Transmissible vaccines offer a novel approach to suppressing viruses in wildlife populations, with possible applications against viruses that infect humans as zoonoses - Lassa, Ebola, rabies. To ensure safety, current designs propose a recombinant vector platform in which the vector is isolated from the target wildlife population. Because using an endemic vector creates the potential for preexisting immunity to block vaccine transmission, these designs focus on vector viruses capable of superinfection, spreading throughout the host population following vaccination of few individuals.
AREAS COVERED
We present original theoretical arguments that, regardless of its R value, a recombinant vaccine using a superinfecting vector is not expected to expand its active infection coverage when released into a wildlife population that already carries the vector. However, if superinfection occurs at a high rate such that individuals are repeatedly infected throughout their lives, the immunity footprint in the population can be high despite a low incidence of active vaccine infections. Yet we provide reasons that the above expectation is optimistic.
EXPERT OPINION
High vaccine coverage will typically require repeated releases or release into a population lacking the vector, but careful attention to vector choice and vaccine engineering should also help improve transmissible vaccine utility.
Topics: Humans; Animals; Superinfection; Rabies; Zoonoses; Rabies Vaccines; Vaccines, Synthetic; Viruses
PubMed: 38372241
DOI: 10.1080/14760584.2024.2320845 -
BMC Microbiology Feb 2024Colistin and carbapenem-resistant Klebsiella pneumoniae (Col-CRKP) represent a significant and constantly growing threat to global public health. We report here an...
BACKGROUND
Colistin and carbapenem-resistant Klebsiella pneumoniae (Col-CRKP) represent a significant and constantly growing threat to global public health. We report here an outbreak of Col-CRKP infections during the fifth wave of COVID-19 pandemic.
METHODS
The outbreak occurred in an intensive care unit with 22 beds at a teaching university hospital, Isfahan, Iran. We collected eight Col-CRKP strains from seven patients and characterized these strains for their antimicrobial susceptibility, determination of hypermucoviscous phenotype, capsular serotyping, molecular detection of virulence and resistance genes. Clonal relatedness of the isolates was performed using MLST.
RESULTS
The COVID-19 patients were aged 24-75 years with at least 50% pulmonary involvement and were admitted to the intensive care unit. They all had superinfection caused by Col-CRKP, and poor responses to antibiotic treatment and died. With the exception of one isolate that belonged to the ST11, all seven representative Col-CRKP strains belonged to the ST16. Of these eight isolates, one ST16 isolate carried the iucA and ybtS genes was identified as serotype K20 hypervirulent Col-CRKP. The bla and bla genes were the most prevalent resistance genes, followed by bla and bla and bla genes. Mobilized colistin-resistance genes were not detected in the isolates.
CONCLUSIONS
The continual emergence of ST16 Col-CRKP strains is a major threat to public health worldwide due to multidrug-resistant and highly transmissible characteristics. It seems that the potential dissemination of these clones highlights the importance of appropriate monitoring and strict infection control measures to prevent the spread of resistant bacteria in hospitals.
Topics: Humans; Colistin; Iran; beta-Lactamases; Klebsiella pneumoniae; Carbapenems; Multilocus Sequence Typing; Pandemics; Klebsiella Infections; Microbial Sensitivity Tests; Anti-Bacterial Agents; Disease Outbreaks; Carbapenem-Resistant Enterobacteriaceae; Hospitals, University; Interleukins
PubMed: 38368365
DOI: 10.1186/s12866-024-03207-6 -
The Journal of Veterinary Medical... Apr 2024Pestiviruses are classified into two biotypes based on their cytopathogenicity. As the majority of pestivirus field isolates are noncytopathogenic, their titration...
Pestiviruses are classified into two biotypes based on their cytopathogenicity. As the majority of pestivirus field isolates are noncytopathogenic, their titration requires alternative methods rather than direct observation of cytopathogenic effects, such as immunostaining using specific antibodies or interference with cytopathogenic strains. However, these methods require microscopic observation to assess virus growth, which is time- and labor-intensive, especially when handling several samples. In this study, we developed a novel luciferase-based pestivirus titration method using the superinfection exclusion phenomenon with recombinant reporter pestiviruses that possessed an 11-amino-acid subunit derived from NanoLuc luciferase (HiBiT). In this method, swine kidney cells were inoculated with classical swine fever virus (CSFV) and superinfected with the reporter CSFV vGPE/HiBiT 5 days postinoculation. Virus titer was determined based on virus growth measured in luminescence using the culture fluid 3 days after superinfection; the resultant virus titer was comparable to that obtained by immunoperoxidase staining. Furthermore, this method has proven to be applicable for the titration of border disease virus (BDV) by superinfection with both the homologous reporter BDV and heterologous reporter CSFV, suggesting that this novel virus titration method is a simple technique for automated virus detection based on the luciferase system.
Topics: Animals; Swine; Pestivirus; Superinfection; Classical Swine Fever Virus; Luciferases; Swine Diseases
PubMed: 38355118
DOI: 10.1292/jvms.24-0005 -
Cureus Jan 2024Mpox (monkeypox) is a zoonotic disease that has been endemic in African countries for decades, with a recent global outbreak in countries around the world. A...
Mpox (monkeypox) is a zoonotic disease that has been endemic in African countries for decades, with a recent global outbreak in countries around the world. A 39-year-old male with human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfection and poor adherence to antiretroviral treatment, who was severely immunocompromised and had a concurrent diagnosis of Mpox, presented to our hospital with disseminated skin lesions (over 350 lesions), perianal ulcers, odynophagia, oral intolerance, diarrhea, and soft-tissue bacterial superinfection of the lower extremities. Laboratory results were consistent with HBV infection, with an absolute CD4 cell count of 40 cells/uL and a positive PCR result for monkeypox virus. An abdominopelvic CT scan showed evidence of severe proctitis and perineal soft-tissue infection. Sixty-five days after a positive monkeypox virus PCR, new lesions in the vesicular stage continued to appear, eventually developing hemodynamic instability and sepsis, resulting in a fatal outcome. Our case highlights the importance of intentionally looking for risk factors such as HIV/HBV coinfection and evaluating immune status (CD4 cell count) in patients with severe Mpox because it could be related to higher mortality.
PubMed: 38344579
DOI: 10.7759/cureus.52043 -
EMBO Reports Mar 2024Human rhinovirus is the most frequently isolated virus during severe exacerbations of chronic respiratory diseases, like chronic obstructive pulmonary disease. In this...
Human rhinovirus is the most frequently isolated virus during severe exacerbations of chronic respiratory diseases, like chronic obstructive pulmonary disease. In this disease, alveolar macrophages display significantly diminished phagocytic functions that could be associated with bacterial superinfections. However, how human rhinovirus affects the functions of macrophages is largely unknown. Macrophages treated with HRV16 demonstrate deficient bacteria-killing activity, impaired phagolysosome biogenesis, and altered intracellular compartments. Using RNA sequencing, we identify the small GTPase ARL5b to be upregulated by the virus in primary human macrophages. Importantly, depletion of ARL5b rescues bacterial clearance and localization of endosomal markers in macrophages upon HRV16 exposure. In permissive cells, depletion of ARL5b increases the secretion of HRV16 virions. Thus, we identify ARL5b as a novel regulator of intracellular trafficking dynamics and phagolysosomal biogenesis in macrophages and as a restriction factor of HRV16 in permissive cells.
Topics: Humans; Rhinovirus; Macrophages; Macrophages, Alveolar; Phagocytosis; Bacteria
PubMed: 38332148
DOI: 10.1038/s44319-024-00069-x -
Revista Da Sociedade Brasileira de... 2024
Topics: Female; Humans; Superinfection; Teratoma; Ovarian Neoplasms; Brucellosis
PubMed: 38324816
DOI: 10.1590/0037-8682-0521-2023 -
The Lancet. Microbe Mar 2024Viral respiratory tract infections are frequently complicated by secondary bacterial infections. This study aimed to use machine learning to predict the risk of... (Observational Study)
Observational Study
BACKGROUND
Viral respiratory tract infections are frequently complicated by secondary bacterial infections. This study aimed to use machine learning to predict the risk of bacterial superinfection in SARS-CoV-2-positive individuals.
METHODS
In this prospective, multicentre, observational cohort study done in nine centres in six countries (Australia, Indonesia, Singapore, Italy, Czechia, and France) blood samples and RNA sequencing were used to develop a robust model of predicting secondary bacterial infections in the respiratory tract of patients with COVID-19. Eligible participants were older than 18 years, had known or suspected COVID-19, and symptoms of a recent respiratory infection. A control cohort of participants without COVID-19 who were older than 18 years and with no infection symptoms was also recruited from one Australian centre. In the pre-analysis phase, data were filtered to include only individuals with complete blood transcriptomics and patient data (ie, age, sex, location, and WHO severity score at the time of sample collection). The dataset was then divided randomly (4:1) into a training set (80%) and a test set (20%). Gene expression data in the training set and control cohort were used for differential expression analysis. Differentially expressed genes, along with WHO severity score, location, age, and sex, were used for feature selection with least absolute shrinkage and selection operator (LASSO) in the training set. For LASSO analysis, samples were excluded if gene expression data were not obtained at study admission, no longitudinal clinical information was available, a bacterial infection at the time of study admission was present, or a fungal infection in the absence of a bacterial infection was detected. LASSO regression was performed using three subsets of predictor variables: patient data alone, gene expression data alone, or a combination of patient data and gene expression data. The accuracy of the resultant models was tested on data from the test set.
FINDINGS
Between March, 2020, and October, 2021, we recruited 536 SARS-CoV-2-positive individuals and between June, 2013, and January, 2020, we recruited 74 participants into the control cohort. After prefiltering analysis and other exclusions, samples from 158 individuals were analysed in the training set and 47 in the test set. The expression of seven host genes (DAPP1, CST3, FGL2, GCH1, CIITA, UPP1, and RN7SL1) in the blood at the time of study admission was identified by LASSO as predictive of the risk of developing a secondary bacterial infection of the respiratory tract more than 24 h after study admission. Specifically, the expression of these genes in combination with a patient's WHO severity score at the time of study enrolment resulted in an area under the curve of 0·98 (95% CI 0·89-1·00), a true positive rate (sensitivity) of 1·00 (95% CI 1·00-1·00), and a true negative rate (specificity) of 0·94 (95% CI 0·89-1·00) in the test cohort. The combination of patient data and host transcriptomics at hospital admission identified all seven individuals in the training and test sets who developed a bacterial infection of the respiratory tract 5-9 days after hospital admission.
INTERPRETATION
These data raise the possibility that host transcriptomics at the time of clinical presentation, together with machine learning, can forward predict the risk of secondary bacterial infections and allow for the more targeted use of antibiotics in viral infection.
FUNDING
Snow Medical Research Foundation, the National Health and Medical Research Council, the Jack Ma Foundation, the Helmholtz-Association, the A2 Milk Company, National Institute of Allergy and Infectious Disease, and the Fondazione AIRC Associazione Italiana per la Ricerca contro il Cancro.
Topics: Humans; COVID-19; SARS-CoV-2; Prospective Studies; Australia; Cohort Studies; Bacterial Infections; Gene Expression Profiling; Machine Learning; Fibrinogen
PubMed: 38310908
DOI: 10.1016/S2666-5247(23)00363-4 -
Heliyon Jan 2024Since 2020, cases of COVID-19-associated pulmonary aspergillosis (CAPA) have been frequently described, representing an important cause of mortality, especially among...
Since 2020, cases of COVID-19-associated pulmonary aspergillosis (CAPA) have been frequently described, representing an important cause of mortality, especially among patients admitted to intensive care unit (ICU). A predisposition to invasive infection caused by spp. in SARS-CoV-2 infected patients can be ascribed either to the direct viral-mediated damage of the respiratory epithelium or to the dysregulated immunity associated with COVID-19. In this case series we have collected the clinical, laboratory and radiological data of 10 patients admitted to the ICU with diagnosis of probable CAPA, according to the recent expert consensus statement, from March 2020 to December 2022 in the Teaching Hospital of Catanzaro in Italy. Overall, 249 patients were admitted to the COVID-19-ICU from March 2020 to December 2022; out of these, 4% developed a probable CAPA. Most of patients were male with a mean age of 62 years. Only two patients had an underlying immunocompromising condition. The observed mortality was 70%. In our institution, all COVID-19 patients requiring invasive mechanical ventilation systematically underwent bronchoscopy with bronchoalveolar lavage for an early evaluation of bacterial and/or fungal co- or super-infections, including galactomannan test. Patients were re-evaluated by an infectious diseases consultant team every 24-48 hours and the galactomannan test was systematically repeated based on patient's clinical course. Even though the numbers in this study are very small, we report our experience about the role of early diagnosis and careful choice of antifungal therapy, considering the fragility of these patients, and its relationship with outcomes. Despite a systemic approach allowing early diagnosis and initiation of anti-fungal therapy, the mortality rate turned out to be very high (70%).
PubMed: 38293516
DOI: 10.1016/j.heliyon.2024.e24298 -
PNAS Nexus Jan 2024[This corrects the article DOI: 10.1093/pnasnexus/pgac187.].
[This corrects the article DOI: 10.1093/pnasnexus/pgac187.].
PubMed: 38292547
DOI: 10.1093/pnasnexus/pgad468