BackgroundKidney transplant recipients receive maintenance immunosuppressive therapy to avoid allograft rejection resulting in increased risk of infections and infection-related morbidity and mortality. Approximately 98% of adults are infected with varicella zoster virus, which upon reactivation causes herpes zoster. The incidence of herpes zoster is higher in kidney transplant recipients than in immunocompetent individuals, and kidney transplant recipients are at increased risk of severe herpes zoster-associated disease. Vaccination with adjuvanted recombinant glycoprotein E subunit herpes zoster vaccine (RZV) prevents herpes zoster in older adults with excellent efficacy (90%), and vaccination of kidney transplant candidates is recommended in Danish and international guidelines. However, the robustness and duration of immune responses after RZV vaccination, as well as the optimal timing of vaccination in relation to transplantation remain unanswered questions. Thus, the aim of this study is to characterize the immune response to RZV vaccination in kidney transplant candidates and recipients at different timepoints before and after transplantation.MethodsThe Herpes Virus Infections in Kidney Transplant Patients (HINT) study is a prospective observational cohort study. The study will include kidney transplant candidates on the waiting list for transplantation (n = 375) and kidney transplant recipients transplanted since January 1, 2019 (n = 500) from all Danish kidney transplant centers who are offered a RZV vaccine as routine care. Participants are followed with repeated blood sampling until 12 months after inclusion. In the case of transplantation or herpes zoster disease, additional blood samples will be collected until 12 months after transplantation. The immune response will be characterized by immunophenotyping and functional characterization of varicella zoster virus-specific T cells, by detection of anti-glycoprotein E antibodies, and by measuring cytokine profiles.DiscussionThe study will provide new knowledge on the immune response to RZV vaccination in kidney transplant candidates and recipients and the robustness and duration of the response, potentially enhancing preventive strategies against herpes zoster in a population at increased risk.Trial registrationClinicalTrials.gov (NCT05604911).

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), can lead to hospitalisation, particularly in elderly, immunocompromised, and non-vaccinated or partially vaccinated individuals. Although vaccination provides protection, the duration of this protection wanes over time. Additional doses can restore immunity, but the influence of viral variants, specific sequences, and vaccine-induced immune responses on disease severity remains unclear. Moreover, the efficacy of therapeutic interventions during hospitalisation requires further investigation. The study aims to analyse the clinical course of COVID-19 in hospitalised patients, taking into account SARS-CoV-2 variants, viral sequences, and the impact of different vaccines. The primary outcome is all-cause in-hospital mortality, while secondary outcomes include admission to intensive care unit and length of stay, duration of hospitalisation, and the level of respiratory support required.MethodsThis ongoing multicentre study observes hospitalised adult patients with confirmed SARS-CoV-2 infection, utilising a combination of retrospective and prospective data collection. It aims to gather clinical and laboratory variables from around 35,000 patients, with potential for a larger sample size. Data analysis will involve biostatistical and machine-learning techniques. Selected patients will provide biological material. The study started on October 14, 2021 and is scheduled to end on October 13, 2026.DiscussionThe analysis of a large sample of retrospective and prospective data about the acute phase of SARS CoV-2 infection in hospitalised patients, viral variants and vaccination in several European and non-European countries will help us to better understand risk factors for disease severity and the interplay between SARS CoV-2 variants, immune responses and vaccine efficacy. The main strengths of this study are the large sample size, the long study duration covering different waves of COVID-19 and the collection of biological samples that allows future research.Trial registrationThe trial has been registered on ClinicalTrials.gov. The unique identifier assigned to this trial is NCT05463380.

BackgroundChronic cholecystitis, characterized by persistent inflammation of the gallbladder, predominantly stems from the prolonged presence of gallstones. Calculous cholecystitis has demonstrated a consistent escalation in its incidence over time.Gallbladder stones have been recognized as a predisposing factor for the development of biliary tract infections.Concomitantly, there have been substantial shifts in the distribution and resistance profiles of pathogenic microorganisms responsible for biliary tract infections. The timely acquisition of bile samples for pathogen analysis is of paramount importance, given its critical role in guiding judicious clinical pharmacotherapy and enhancing patient prognosis.Case PresentationWe present a case involving a 66-year-old female patient who had previously undergone subtotal gastrectomy due to diffuse large B-cell lymphoma. The patient was admitted to our institution with complaints of abdominal pain. Subsequent diagnostic evaluation revealed concurrent choledocholithiasis and cholecystolithiasis. The patient underwent surgical cholecystectomy as the therapeutic approach. Histopathological examination of the excised gallbladder disclosed characteristic features indicative of chronic cholecystitis. Subsequent laboratory analysis of the patient’s bile specimen yielded Gram-positive cocci, subsequently identified through biochemical assays, mass spectrometry, and 16 S rRNA analysis as Vagococcus fluvialis. Further in vitro antimicrobial susceptibility testing using disk diffusion and microfluidic dilution showed that this strain exhibited inhibition zone diameters ranging from 12.0 to 32.0 mm in response to 26 antibiotics, including ampicillin, cefazolin, cefuroxime, cefotaxime, ceftriaxone, cefepime, ampicillin/sulbactam, piperacillin, ciprofloxacin, cefoperazone/sulbactam, imipenem, meropenem, piperacillin/tazobarb, penicillin, erythromycin, chloramphenicol, vancomycin, methotrexate/sulfamethoxazole, teicoplanin, linezolid, tigecycline, cefoxitin, ceftazidime, levofloxacin, minocycline and tobramycin. However, the inhibition zone diameters were 6.0 mm for amikacin, oxacillin, clindamycin, and tetracycline. The patient received ceftazidime anti-infective therapy both preoperatively and within 24 h postoperatively and was discharged successfully one week after surgery.ConclusionIn this study, we present the inaugural isolation and identification of Vagococcus fluvialis from bile specimens of patients afflicted with calculous cholecystitis. This novel finding lays a substantial experimental groundwork for guiding clinically rational antimicrobial therapy and advancing the exploration of relevant pathogenic mechanisms pertaining to Vagococcus fluvialis infections.

BackgroundWhile laboratory testing for infectious diseases such as COVID-19 is the surveillance gold standard, it is not always feasible, particularly in settings where resources are scarce. In the small country of Lesotho, located in sub-Saharan Africa, COVID-19 testing has been limited, thus surveillance data available to local authorities are limited. The goal of this study was to compare a participatory influenza-like illness (ILI) surveillance system in Lesotho with COVID-19 case count data, and ultimately to determine whether the participatory surveillance system adequately estimates the case count data.MethodsA nationally-representative sample was called on their mobile phones weekly to create an estimate of incidence of ILI between July 2020 and July 2021. Case counts from the website Our World in Data (OWID) were used as the gold standard to which our participatory surveillance data were compared. We calculated Spearman’s and Pearson’s correlation coefficients to compare the weekly incidence of ILI reports to COVID-19 case count data.ResultsOver course of the study period, an ILI symptom was reported 1,085 times via participatory surveillance for an average annual cumulative incidence of 45.7 per 100 people (95% Confidence Interval [CI]: 40.7 – 51.4). The cumulative incidence of reports of ILI symptoms was similar among males (46.5, 95% CI: 39.6 – 54.4) and females (45.1, 95% CI: 39.8 – 51.1). There was a slightly higher annual cumulative incidence of ILI among persons living in peri-urban (49.5, 95% CI: 31.7 – 77.3) and urban settings compared to rural areas. The January peak of the participatory surveillance system ILI estimates correlated significantly with the January peak of the COVID-19 case count data (Spearman’s correlation coefficient = 0.49; P < 0.001) (Pearson’s correlation coefficient = 0.67; P < 0.0001).ConclusionsThe ILI trends captured by the participatory surveillance system in Lesotho mirrored trends of the COVID-19 case count data from Our World in Data. Public health practitioners in geographies that lack the resources to conduct direct surveillance of infectious diseases may be able to use cell phone-based data collection to monitor trends.

BackgroundThe intravenous form of fosfomycin, a bactericide antibiotic used to treat multiresistant bacterial infections is little prescribed. The most common reported adverse effects are hypokaliemia and hypernatremia. We describe a case of agranulocytosis, a rarely described side effect that may be fatal.Case presentationA 45 year-old woman was admitted to the intensive care unit for post-surgical meningitis following meningioma resection. Meropenem and vancomycin were first introduced. A DRESS-syndrom with meropenem was suspected. Neutropenia was diagnosed three days after the introduction of parenteral fosfomycin and agranulocytosis four days later. Eosinophilia was also observed. A bone marrow aspiration was performed showing a disappearance of the neutrophil granulocyte line and a significant eosinophilia. Meropenem was discontinued. Fosfomycin was maintained and filgrastim was added. As filgrastim had no effect, the relationship with fosfomycin was suspected, so it was then withheld. An increase of the neutrophil count was observed. Because of the complexity of the case, the unfavorable course of the illness and the urgent need for revision surgery, a rechallenge with fosfomycin was done followed by a decrease of the neutrophil count.ConclusionThis is the third paper reporting agranulocytosis induced by fosfomycin, and the first detailed description of a case. Based on chronological and semiological criteria and bibliographic data, the event was qualified as probable with the Naranjo adverse drug probability scale. Literature data is scarce. The summary of product characteristics mentions that only a few cases of transient neutropenia and agranulocytosis have been reported. An analysis of the FDA Adverse Event Reporting System Database highlighted a higher than expected frequency of agranulocytosis in patients treated with fosfomycin. Parenteral fosfomycin is often used in patients receiving other medications, so that it is rarely the only suspect. In our case, the results of the bone marrow aspiration, the sudden drop of the neutrophil count with concomitant eosinophilia and the absence of improvement despite the dose decrease, point towards an immuno-allergic mechanism. However, the overlap between the suspected DRESS induced by meropenem and the agranulocytosis do not allow to conclude with certainty on the causality. Awareness should be raised about this side effect.

BackgroundNosocomial infections or hospital-acquired infections are a growing public health threat that increases patient morbidity and mortality. Patients at the highest risk are those in intensive care units. Therefore, our objective was to provide a pattern analysis of nosocomial infections that occurred in an adult surgical intensive care unit (ICU).MethodsThis study was a retrospective observational study conducted in a 6-bed surgical intensive care unit (SICU) at An-Najah National University Hospital (NNUH) to detect the incidence of nosocomial infections from January 2020 until December 2021. The study group included 157 patients who received antibiotics during their stay in the SICU.ResultsThe incidence of nosocomial infections, either suspected or confirmed, in the SICU was 26.9% (95 out of 352 admitted patients). Pneumonia (36.8%) followed by skin and soft tissue infections (35.8%) were the most common causes. The most common causative microorganisms were in the following order: Pseudomonas aeruginosa (26.3%), Acinetobacter baumannii (25.3%), extended-spectrum beta lactamase (ESBL)-Escherichia coli (23.2%) and Klebsiella pneumonia (15.8%). The average hospital stay of patients with nosocomial infections in the SICU was 18.5 days.ConclusionsThe incidence of nosocomial infections is progressively increasing despite the current infection control measures, which accounts for an increased mortality rate among critically ill patients. The findings of this study may be beneficial in raising awareness to implement new strategies for the surveillance and prevention of hospital-acquired infections in Palestinian hospitals and health care centers.

BackgroundPost-COVID-19 condition refers to persistent or new onset symptoms occurring three months after acute COVID-19, which are unrelated to alternative diagnoses. Symptoms include fatigue, breathlessness, palpitations, pain, concentration difficulties ("brain fog"), sleep disorders, and anxiety/depression. The prevalence of post-COVID-19 condition ranges widely across studies, affecting 10–20% of patients and reaching 50–60% in certain cohorts, while the associated risk factors remain poorly understood.MethodsThis multicentre cohort study, both retrospective and prospective, aims to assess the incidence and risk factors of post-COVID-19 condition in a cohort of recovered patients. Secondary objectives include evaluating the association between circulating SARS-CoV-2 variants and the risk of post-COVID-19 condition, as well as assessing long-term residual organ damage (lung, heart, central nervous system, peripheral nervous system) in relation to patient characteristics and virology (variant and viral load during the acute phase). Participants will include hospitalised and outpatient COVID-19 patients diagnosed between 01/03/2020 and 01/02/2025 from 8 participating centres. A control group will consist of hospitalised patients with respiratory infections other than COVID-19 during the same period.Patients will be followed up at the post-COVID-19 clinic of each centre at 2–3, 6–9, and 12–15 months after clinical recovery. Routine blood exams will be conducted, and patients will complete questionnaires to assess persisting symptoms, fatigue, dyspnoea, quality of life, disability, anxiety and depression, and post-traumatic stress disorders.DiscussionThis study aims to understand post-COVID-19 syndrome's incidence and predictors by comparing pandemic waves, utilising retrospective and prospective data. Gender association, especially the potential higher prevalence in females, will be investigated. Symptom tracking via questionnaires and scales will monitor duration and evolution. Questionnaires will also collect data on vaccination, reinfections, and new health issues. Biological samples will enable future studies on post-COVID-19 sequelae mechanisms, including inflammation, immune dysregulation, and viral reservoirs.Trial registrationThis study has been registered with ClinicalTrials.gov under the identifier NCT05531773.

BackgroundBacteria account for nearly one third of the causes of community-acquired central nervous system infections, and traditional diagnostic methods are based on culture results, which are time-consuming and have a low detection rate leading to delayed diagnosis and treatment. Since metagenomic next-generation sequencing (mNGS) has the advantages of high timeliness and only detecting microbial trace gene fragments, it has been used more widely in recent years. Based on this, we explored whether the application of cerebrospinal fluid (CSF) mNGS is advantageous in patients with community-acquired purulent meningitis, especially in people who have already used antibiotics.MethodsThis was a retrospective study of 63 patients with community-acquired purulent meningitis admitted to the Department of Neurology of Shanxi Bethune Hospital from March 2018 to November 2022. Data were systematically collected and classified into CSF culture group, blood culture group and CSF mNGS group according to different detection methods, and the total detection rate of each method was calculated. Each group of patients was divided into two subgroups according to whether antibiotics were used before sampling. The detection rates of the three groups were compared within and between groups to explore whether mNGS has advantages over traditional methods and the influence of antibiotic use on detection rates of the three methods.ResultsAmong the 63 patients, the cases of CSF culture, blood culture and CSF mNGS were 56, 46, 44, respectively. The total detection rates of the three methods were 17.86%, 36.96%, 81.82%, with statistical differences (p < 0.05),suggesting that the detection rate of mNGS was higher than CSF culture (p < 0.05) and blood culture (p < 0.05),and the detection rate of blood culture higher than CSF culture (p < 0.05). Further grouping found that without antibiotics, the detection rates of CSF culture, blood culture and CSF mNGS were 28.57%, 56.25% and 88.89%, with statistical differences (p < 0.05), and the detection rate of CSF mNGS was higher than that of CSF culture (p < 0.05), but there was no statistical difference between CSF and blood culture (p > 0.05), nor between blood culture and CSF mNGS (p > 0.05). The detection rates of the three groups with antibiotics were 14.29%, 26.67% and 80.00%, with statistical differences (p < 0.05), and the detection rate of CSF mNGS was still higher than CSF culture (p < 0.05) and blood culture (p < 0.05). However, the detection rate of CSF mNGS also decreased after antibiotics were used for more than 3 days.ConclusionsThe detection rate of CSF mNGS in patients with purulent meningitis is higher than traditional methods, especially in patients who have been given antibiotics, but the detection rate will decrease with the extension of antibiotic use.

BackgroundPneumonia is the leading infectious cause of mortality worldwide and one of the most common lower respiratory tract infections that is contributing significantly to the burden of antibiotic consumption. The study aims to identify the determinants of the progress of pulse rate, body temperature and time to recovery of pneumonia patients.MethodA prospective cohort study design was used from Felege Hiwot referral hospital on 214 sampled pneumonia patients from March 01, 2022 up to May 31, 2022. The Kaplan–Meier survival estimate and Log-Rank test was used to compare the survival time. Joint model of bivariate longitudinal and time to event model was used to identify factors of longitudinal change of pulse rate and body temperature with time to recovery jointly.ResultAs the follow up time of pneumonia patient’s increase by one hour the average longitudinal change of pulse rate and body temperature were decreased by 0.4236 bpm and 0.0119 {C}^{0}. The average longitudinal change of pulse rate and body temperature of patients who lived in rural was 1.4602 bpm and 0.1550 {C}^{0} times less as compared to urban residence. Patients who had dangerous signs are significantly increased the average longitudinal change of pulse rate and body temperature by 2.042 bpm and 0.6031 {C}^{0} as compared to patients who had no dangerous signs. A patient from rural residence was 1.1336 times more likely to experience the event of recovery as compared to urban residence. The estimated values of the association parameter for pulse rate and body temperature were -0.4236 bpm and -0.0119 respectively, which means pulse rate and body temperature were negatively related with patients recovery time.ConclusionPulse rate and body temperature significantly affect the time to the first recovery of pneumonia patients who are receiving treatment. Age, residence, danger sign, comorbidity, baseline symptom and visiting time were the joint determinant factors for the longitudinal change of pulse rate, body temperature and time to recovery of pneumonia patients. The joint model approach provides precise dynamic predictions, widespread information about the disease transitions, and better knowledge of disease etiology.