Search Results (591)

The urgent requirement for swift diagnostic methods in pathogen identification and antimicrobial susceptibility testing is emphasized by rising bacterial resistance and limited treatment options, which are particularly critical in sepsis management. The shift from traditional phenotype-based methods to rapid molecular and mass spectrometry techniques has significantly reduced result turnaround times, enhancing patient outcomes. In this systematic review with meta-analysis, the aspects of correct empirical antimicrobial therapy are evaluated to determine their impact on mortality. We performed a systematic review and meta-analysis on EMBASE, the Cochrane Library, Web of Science, and MEDLINE. Studies evaluating mortality associated with empirical adequate and inadequate therapy in different sites of infection were included. Outcomes included clinical cures in microbiologically evaluable patients. Among the sites of infection, the most studied were bloodstream infections (n = 9), followed by respiratory tract infections (n = 5), intra-abdominal infections (n = 5), and urinary tract infections (evaluated by 3 studies). Inadequate therapy was associated with an increase in mortality between 11 and 68%. Technologies to speed up pathogen identification are extremely necessary to reduce mortality. Full article

Here, we report the simultaneous isolation of Pseudomonas straminea from blood cultures and from a skin ulcer in an elderly woman who suffered from atopic dermatitis and psoriasis and developed acute cellulitis of both arms requiring hospital treatment. To the best of our knowledge, P. straminea has not been previously reported to cause invasive infections in humans. This case highlights how chronic diseases and older age increase the susceptibility to bacterial infections with environmental bacteria of low virulence. Our study describes the microbiological identification of the blood culture isolate, including morpho-molecular characterization and virulence demonstration in a Galleria mellonella model. Full article

Antimicrobial resistance (AMR) is an increasing problem worldwide, with significant associated morbidity and mortality. Given the slow production of new antimicrobials, non-antimicrobial methods for treating infections with significant AMR are required. This review examines the potential of predatory bacteria to combat infectious diseases, particularly those caused by pathogens with AMR. Predatory bacteria already have well-known applications beyond medicine, such as in the food industry, biocontrol, and wastewater treatment. Regarding their potential for use in treating infections, several in vitro studies have shown their potential in eliminating various pathogens, including those resistant to multiple antibiotics, and they also suggest minimal immune stimulation and cytotoxicity by predatory bacteria. In vivo animal studies have demonstrated safety and efficacy in reducing bacterial burden in various infection models. However, results can be inconsistent, suggesting dependence on factors like the animal model and the infecting bacteria. Until now, no clinical study in humans exists, but as experience with predatory bacteria grows, future studies including clinical studies in humans could be designed to evaluate their efficacy and safety in humans, thus leading to the potential for approval of a novel method for treating infectious diseases by bacteria. Full article

Purpose: Effective antimicrobial use enhances care quality and combats antibiotic resistance. Yet, non-guideline factors influence potentially inappropriate prescribing. This study explores psycho-socio-organisational factors in antimicrobial prescribing as perceived by physicians across primary, secondary, and tertiary care. Methods: Adhering to PRISMA guidelines, a systematic review was conducted using PubMed and Scopus databases from 1 January 2000, to 8 March 2023, with an update search until 30 January 2024. Inclusion criteria focused on studies in Europe exploring psycho-socio-organisational factors for antibiotic prescribing from physicians’ perspectives in hospital, inpatient, or primary care settings. Exclusion criteria targeted out-of-office prescriptions or low-quality studies. To evaluate the latter, several quality and risk-of-bias checklists were used. Data were extracted on study characteristics, study design, and methods and identified determinants of antibiotic prescribing. Data was analysed using a narrative synthesis method. Results: Among 8370 articles, 58 met inclusion criteria, yielding 35 articles from 23 countries. Three main themes emerged: personal, psychological, and organisational factors, encompassing seven determinants including work experience, knowledge, guideline adherence, uncertainty management, perceived pressure, time constraints, and diagnostic resource availability. Uncertainty management was key, with work experience and knowledge mitigating it. No additional factors emerged in the updated search. Conclusion: Enhanced uncertainty management decreases perceived patient and/or parental pressure to prescribe antibiotics, contributing to reducing potentially inappropriate prescribing (PIP). Therefore, it is imperative to educate physicians on effectively managing uncertainty. Interventions to improve antibiotic prescribing should be tailored to the specific needs and preferences of the different prescribing physicians. Full article

Chagas disease (CD) is a parasitic infection endemic in Latin America and also affects patients in Western countries due to migration flows. This has a significant impact on health services worldwide due to its high morbidity and mortality burden. This paper aims to share our experience at the National Institute for Infectious Diseases “Lazzaro Spallanzani”, IRCCS, in Rome, Italy, where to date, a total of 47 patients—mainly Bolivian women—diagnosed with CD have received treatment with benznidazole, with all but one presenting with chronic disease. Most of the patients were recruited through the first extensive screening program held in 2014 at our Institute. About a quarter of our patients showed adverse effects to benznidazole, including a case of severe drug-induced liver injury, but 83% completed a full course of treatment. In addition to the description of our cohort, the paper reports a brief overview of the disease compiled through a review of the existing literature on CD in non-endemic countries. The growing prevalence of CD in Western countries highlights the importance of screening at-risk populations and urges public concern and medical awareness about this neglected tropical disease. There are still many unanswered questions that need to be addressed to develop a personalized approach in treating patients. Full article

Leptospirosis is considered to be the most widespread, yet neglected, re-emerging zoonotic disease caused by infection with a pathogenic species of the genus Leptospira. Although this disease is prevalent in Bangladesh, the recent epidemiological status has not yet been well documented. In this study, we aimed to determine the prevalence of leptospirosis among febrile patients using different diagnostic methods and to characterize the epidemiological features and species of Leptospira in Mymensingh, north–central Bangladesh. Among the blood samples of 186 patients with suspected leptospirosis who met the inclusion criteria, including having a fever for more than 5 days (November 2021–June 2022), 88 samples (47%) were Leptospira-positive according to IgM LAT, IgM ELISA, or nested PCR (positivity rates: 38%, 37%, and 42%, respectively). Nested PCR showed a significantly higher positivity rate (54%) in patients with a short fever (5–10 day) than the other methods did, with lower rates among those with a longer fever. Leptospirosis cases were more common in males (68%), those 16–45 years of age (70%), residents of rural areas (81%), and farmers (41%). In addition to a fever, myalgia and jaundice were found in more than 70% of the patients, while variable symptoms were observed. The 16S rRNA sequencing analysis revealed that the Leptospira species in all the 22 samples tested were L. wolffii, belonging to the pathogenic subclade P2. This study showed the recent epidemiological features of leptospirosis in Bangladesh, indicating the presumptive predominance of L. wolffii since 2019. Full article

We describe a case of an immunocompetent adult male patient originally from the Democratic Republic of Congo (DRC), who was referred to our unit for a several-day history of fever and a pruritic, vesicular rash. There was initial concern in the Emergency Department for Mpox (formerly known as “monkeypox”) given the current epidemiology versus other viral etiologies. Primary varicella zoster virus (pVZV) infection was ultimately diagnosed by PCR from a swabbed, unroofed lesion, and he recovered completely with supportive management and without antiviral therapy. We herein describe how common viral exanthems may best be differentiated in an emergency or outpatient setting. Full article

The emergence of SARS-CoV-2 in 2019 led to a global pandemic with a significant impact on healthcare systems. Healthcare workers were particularly vulnerable due to frequent contact with COVID-19 patients. Despite vaccination, they remained at higher risk as the vaccines provided limited protection against infection with viral variants, like Delta or Omicron BA.1 and BA.5. Three years after the onset of the pandemic, we evaluated SARS-CoV-2 infection frequencies among healthcare workers with varying levels of patient contact: high-risk (frequent COVID-19 patient contact), intermediate-risk (non-COVID-19 patient contact), and low-risk (no patient contact). We assessed their cellular and humoral immune responses based on their vaccination status and number of prior infections. SARS-CoV-2-specific antibodies were measured by immunoglobulin ELISA, and neutralizing antibody titers were determined against the viral variants D614G, Delta, and Omicron BA.1 and BA.5. Cellular immune responses were analyzed using an interferon-γ ELISpot. Notably, three years into the pandemic, healthcare workers in daily contact with COVID-19 patients did not have higher infection rates compared to healthcare workers with non-COVID-19 patient contact or no patient contact. Immune responses were similar across all groups, highlighting the effectiveness of vaccination and current hygiene standards in preventing virus transmission from patients to staff. Full article

Background: Bacterial aggregation has been well described to occur in synovial fluid, but it is unknown if bacteria form aggregates in body fluids beyond the synovial fluid. Consequently, this translational study evaluated the ability to form bacterial aggregates in different pleural fluids. Methods: Four of the most common causes of thoracic empyema—Streptococcus mitis, Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa—were used here. The different pleural fluids included one transudative and two exudative pleural fluids. Twenty-four-well microwell plates were used to form the aggregates with the aid of an incubating shaker at different dynamic conditions (120 RPM, 30 RPM, and static). The aggregates were then visualized with SEM and evaluated for antibiotic resistance and the ability of tissue plasminogen activator (TPA) to dissolve the aggregates. Statistical comparisons were made between the different groups. Results: Bacterial aggregates formed at high shaking speeds in all pleural fluid types, but no aggregates were seen in TSB. When a low shaking speed (30 RPM) was used, only exudative pleural fluid with a high protein content formed aggregates. No aggregates formed under static conditions. Furthermore, there was a statistical difference in the CFU/mL of bacteria present after antibiotics were administered compared to bacteria with no antibiotics (p < 0.005) and when TPA plus antibiotics were administered compared to antibiotics alone (p < 0.005). Conclusions: This study shows that bacteria can form aggregates in pleural fluid and at dynamic conditions similar to those seen in vivo with thoracic empyema. Importantly, this study provides a pathophysiological underpinning for the reason why antibiotics alone have a limited utility in treating empyema. Full article

SARS-CoV-2 infection was shown to induce proprotein convertase subtilisin/kexin type 9 (PCSK9) plasma levels in sepsis. Here, we investigate the association between serum PCSK9 levels and disease severity. PCSK9 was measured in serum of 55 controls, 40 patients with moderate and 60 patients with severe COVID-19 disease. Serum PCSK9 was elevated in moderate COVID-19 compared to controls and further increased in severe cases. PCSK9 levels were not associated with C-reactive protein, bacterial superinfections, interventions, or survival in patients with severe COVID-19. PCSK9 regulates circulating cholesterol levels, and 15 cholesteryl ester (CE) species and free cholesterol (FC) were quantified by direct flow injection analysis using a high-resolution hybrid quadrupole-Orbitrap mass spectrometer. Most CE species with shorter fatty acid chains were decreased in severe compared to moderate COVID-19, and none of the CE species were correlated with PCSK9 in patients with severe COVID-19. Levels of all CE species negatively correlated with C-reactive protein in severe COVID-19 patients. Notably, FC was induced in severe compared to moderate COVID-19. The FC/CE ratio correlated positively with inflammatory markers and was associated with non-survival. The current study suggests that the imbalance between CE and FC levels is associated with disease severity and mortality in patients with COVID-19. Full article

Hand, foot, and mouth disease (HFMD) is a common infectious disease caused by enteroviruses. Coxsackievirus A6 (CV-A6)-associated HFMD has recently emerged as a predominant disease worldwide. Here, we describe five HFMD cases caused by CV-A6 in Japan from 2019 to 2022. All clinical courses were not severe and were self-limited, and the skin exanthema with vesicles differed from that in classical HFMD. Phylogenetic analysis showed that the major epidemic strain cluster of CV-A6 was formed independently in 2011, and our latest CV-A6 strains in Japan were detected within this cluster. The five cases described in this report indicate the recent shift in the predominant and continuous disease manifestation of CV-A6-associated HFMD. Full article

The secreted aspartic peptidases (Saps) of Candida albicans play crucial roles in various steps of fungal–host interactions. Using a flow cytometry approach, this study investigated the expression of Saps1–3 antigens after (i) incubation with soluble proteins, (ii) interaction with mammalian cells, and (iii) infection in immunosuppressed BALB/c mice. Supplementation strategies involving increasing concentrations of bovine serum albumin (BSA) added to yeast carbon base (YCB) medium as the sole nitrogenous source revealed a positive and significant correlation between BSA concentration and both the growth rate and the percentage of fluorescent cells (%FC) labeled with anti-Saps1–3 antibodies. Supplementing the YCB medium with various soluble proteins significantly modulated the expression of Saps1–3 antigens in C. albicans. Specifically, immunoglobulin G, gelatin, and total bovine/human sera significantly reduced the %FC, while laminin, human serum albumin, fibrinogen, hemoglobin, and mucin considerably increased the %FC compared to BSA. Furthermore, co-cultivating C. albicans yeasts with either live epithelial or macrophage cells induced the expression of Saps1–3 antigens in 78% (mean fluorescence intensity [MFI] = 152.1) and 82.7% (MFI = 178.2) of the yeast cells, respectively, compared to BSA, which resulted in 29.3% fluorescent cells (MFI = 50.9). Lastly, the yeasts recovered from the kidneys of infected immunosuppressed mice demonstrated a 4.8-fold increase in the production of Saps1–3 antigens (MFI = 246.6) compared to BSA, with 95.5% of yeasts labeled with anti-Saps1–3 antibodies. Altogether, these results demonstrated the positive modulation of Saps’ expression in C. albicans by various key host proteinaceous components, as well as by in vitro and in vivo host challenges. Full article

Angiotensin-converting enzyme 2 (ACE2), a key regulator in vasoregulation and the renin–angiotensin system, is hypothesized to be downregulated in patients with COVID-19, leading to a cascade of cardiovascular complications. This deactivation potentially results in increased blood pressure and vessel injury, contributing to the formation and persistence of microclots in the circulation. Herein, we propose a hypothesis regarding the prolonged vascular complications observed in long COVID, focusing on the role of ACE2 deactivation and/or shedding, the persistence of microclots, and the unique pattern of fibrosis induced by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Furthermore, we propose that the distinctive, uniform fibrosis associated with COVID-19, which is challenging to detect through conventional X-ray imaging, exacerbates vascular injury and impairs oxygenation. The persistence of these microclots and the unique fibrosis pattern are suggested as key factors in the extended duration of vascular complications post-COVID-19 infection, regardless of the initial disease severity. Moreover, plasma ACE2 activity has the potential to serve as prognostic or diagnostic biomarkers for monitoring disease severity and managing long COVID symptoms. Elucidating the role of ACE2 deactivation and the consequent events is vital for understanding the long-term effects of COVID-19. The experimental verification of this hypothesis through in vitro studies, clinical longitudinal studies, and advanced imaging techniques could yield significant insights into the pathophysiological mechanisms underlying long COVID, thereby improving the management of patients, particularly those with cardiovascular complications. Full article

Parasitic diseases, such as malaria, are an immense burden to many low- and middle-income countries. In 2022, 249 million cases and 608,000 deaths were reported by the World Health Organization for malaria alone. Climate change, conflict, humanitarian crises, resource constraints and diverse biological challenges threaten progress in the elimination of malaria. Undeniably, the lack of a commercialized vaccine and the spread of drug-resistant parasites beg the need for novel approaches to treat this infectious disease. Most approaches for the development of antimalarials to date take inspiration from tropical or sub-tropical environments; however, it is necessary to expand our search. In this review, we highlight the origin of antimalarial treatments and propose new insights in the search for developing novel antiparasitic treatments. Plants and microorganisms living in harsh and cold environments, such as those found in the largely unexploited Northern Canadian boreal forest, often demonstrate interesting properties that are not found in other environments. Most prominently, the essential oil of Rhododendron tomentosum spp. Subarcticum from Nunavik and mortiamides isolated from Mortierella species found in Nunavut have shown promising activity against Plasmodium falciparum. Full article

COVID-19, caused by the SARS-CoV-2 virus, is a highly pathogenic emerging infectious disease. Healthcare personnel (HCP) are presumably at higher risk of acquiring emerging infections because of occupational exposure. The prevalence of COVID-19 in HCP is unknown, particularly in low- to middle-income countries like El Salvador. The goal of this study was to determine the seroprevalence of anti-SARS-CoV-2 antibodies among HCP in El Salvador just prior to vaccine rollout in March 2021. We evaluated 2176 participants from a nationally representative sample of national healthcare institutions. We found 40.4% (n = 880) of the study participants were seropositive for anti-spike protein antibodies. Significant factors associated with infection included younger age; living within the central, more populated zone of the country; living in a larger household (≥7 members); household members with COVID-19 or compatible symptoms; and those who worked in auxiliary services (i.e., housekeeping and food services). These findings provide insight into opportunities to mitigate SARS-CoV-2 risk and other emerging respiratory pathogens in HCP in El Salvador. Full article