Infectious diseases (London, England)最新文献

Background: The study aimed to describe all diagnosed cases of Legionnaire's disease (LD) in south Sweden, regarding incidence, patient characteristics, diagnostics, outcomes, and infection control investigations.

Methods: This population-based retrospective study was conducted in Skåne, on patients with LD between 2011-2021. Inclusion criteria were positive polymerase chain reaction (PCR) for L. pneumophila/Legionella spp. or a positive urinary antigen test (UAT), combined with a clinical presentation consistent with Legionella infection and radiological evidence of pulmonary infiltrates.

Results: A total of 280 patients met the inclusion criteria, with a mean incidence of 2.00 per 100,000 person-years (95% CI: 1.23-2.78). Empiric treatment covering Legionella was administered in 15% of cases. Mortality rates were 13%, 15% and 23% at 30-, 90- and 365 days, respectively. UAT was performed in 88% of patients, with a 66% positivity rate. Lower respiratory tract PCR was performed in 76% of patients with a 90% positivity rate. Bacterial culture was positive in 43% of cases. Out of these, L. pneumophila serogroup 1 was most common (58%), though a significant proportion were serogroups 2-14 (30%), which are not generally detected by UAT. Genetic matches between environmental and patient strains were established in 5% of cases.

Conclusion: Legionnaires' disease in Skåne is an uncommon but clinically significant condition. Few patients received appropriate empiric antibiotic treatment. Reliance on UAT alone is insufficient for establishing diagnosis, and species-specific PCR, particularly from lower respiratory samples, enhances detection. Environmental investigations frequently identified Legionella in suspected settings; however, a definitive source of infection was rarely established.

Background: In May 2023, the World Health Organization declared COVID-19 no longer a public health emergency. Despite successful vaccination campaigns, vaccines provide limited protection against transmission. Since general testing has been abandoned in most countries, alternative population surveillance methods to assess SARS-CoV-2 exposure are needed.

Methods: N-antigen is a protein of the SARS-CoV-2 virus that is not present in the vaccines and hence may be a useful serological marker of infection. This study evaluated N-antigen antibodies as a marker of SARS-CoV-2 exposure in a vaccinated Swedish cohort. Serum samples were collected and analysed for N-antigen antibodies using the mesoscale system. Nonlinear mixed-effects model accounting for multiple measurements per individual was used to estimate the half-life of N-antigen antibodies.

Results: A total of 3,202 participants (median age 31 years) were recruited from April 2021 to February 2022 from four vaccination centres in Skåne, Sweden. A total of 2,999 participants had at least one valid N-antigen antibody measurement. The estimated half-life of N-antigen antibodies was 59 days (95% CI: 55-64 days). The estimated 95% range of halves-lives were from 24 to 174 days. The repeated measurements of N-antigen antibody levels could accurately detect SARS-CoV-2 infection. A twofold increase had a sensitivity of 91%, whereas a 16-fold increase had a specificity of 91%, respectively. The area under the curve (AUC) for predicting infection was 0.88 [95% C.I. 0.86-0.90].

Conclusion: Repeated monitoring of N-antigen antibody levels may be a valuable tool for assessing SARS-CoV-2 exposure and thus aid in monitoring transmission thereby helping in guiding vaccination strategies.

Background: Norovirus causes an estimated 699 million cases of gastroenteritis and 219,000 deaths each year. Historically, novel strains with a genogroup II genotype 4 (GII.4) capsid have emerged every 3-5 years to cause gastroenteritis pandemics. Contrary to historical trends, viruses with aGII.4 Sydney 2012 capsid have extended the timeframe of capsid circulation, well beyond the usual 3-5 years, through genetic recombination to obtain new non-structural regions, for example, a GII.P16 ORF1.

Objectives and methods: The molecular evolution in the GII.4 capsid of strains in New South Wales (NSW), Australia and New Zealand (NZ) before and into the COVID-19 pandemic (2018-20) was investigated by sequencing noroviruses from clinical specimens and wastewater.

Results: A continued high prevalence of GII.4 Sydney 2012 [P16] was observed (NSW: 23.0%; NZ: 24.2%), albeit co-dominant with GII.2 [P16] (NSW: 20.2%; NZ: 29.4%). Unlike the historical trends, the GII.4 Sydney 2012 capsid has been in circulation for eight years. Circulating norovirus in the community was disrupted by COVID-19 control measures; lockdowns reduced viral concentration in wastewater by >90% (1.4 × 10⁵ genome copies (gc)/L) from May to September 2020 compared to equivalent timeframes in 2018 (1.6 × 10⁶gc/L) and 2019 (1.9 × 10⁶gc/L). The relaxation of lockdown measures in late-2020 coincided with a strong resurgence of GII.2[P16] prevalence both clinically and in wastewater in NSW and Melbourne, accompanied by a decline in the diversity of circulating noroviruses. Conclusion: In summary, COVID-19 disrupted the strain diversity and levels of norovirus in Australia and New Zealand.

Background: Bacterial confirmation in suspected tuberculosis lymphadenitis patients is challenging. This study evaluates plasma Mycobacterium tuberculosis cell-free DNA as a diagnostic tool for tuberculosis lymphadenitis.

Methods: A quantitative PCR assay targeting IS6110, IS1081, and cyp141 genes was performed on plasma samples. The study included 95 tuberculosis lymphadenitis patients and 60 controls. Sensitivity of the plasma Mycobacterium tuberculosis cell-free DNA assay was assessed against fine needle aspiration GeneXpert Ultra, fine needle aspiration culture, and fine needle aspiration cytology, while specificity was determined using control groups.

Results: Of the tuberculosis lymphadenitis cases, 71 (74.7%) were bacteriologically confirmed, and 24 (25.3%) were probable. In the control group, 50% had latent tuberculosis infection. The Mycobacterium tuberculosis cell-free DNA assay, targeting three genes, had an overall sensitivity of 65.3%, increasing to 70.4% for confirmed cases and 50% for probable cases, with specificity of 91.1%. Sensitivities for specific gene combinations were 62.1% for IS6110 and IS1081, 54.7% for IS6110 and cyp141, and 55.8% for IS1081 and cyp141. For individual genes, IS6110 showed 49.4% sensitivity (specificity: 93.3%), IS1081 had 51.6% (specificity: 96.0%), and cyp141 showed 28.4% (specificity: 96.7%). Combining positive results from all three genes in the cell-free DNA assay with fine needle aspiration culture and GeneXpert Ultra improved sensitivity to 76.8% and 85.3%, respectively.

Conclusion: This study demonstrated that Mycobacterium tuberculosis cell-free DNA can be detected in the plasma of over half of tuberculosis lymphadenitis patients. The plasma Mycobacterium tuberculosis cell-free DNA assay could serve as a valuable, less-invasive complement to existing fine needle aspiration diagnostics.

Introduction: Candida albicans is the most frequent fungal organism causing vertebral spondylodiskitis. Given limited research, this study aimed to describe patient characteristics, treatment, and outcomes of the C. albicans spondylodiscitis patients in Southern Denmark using a case series and literature review.

Methods: We conducted a retrospective review of all consecutive patients treated for infectious spondylodiscitis during 2009-2023 at the Department of Infectious Diseases, Odense University Hospital, Denmark. All medical records were reviewed and cases of C. albicans were included. A review of the English literature from the last decade was conducted with a predefined search string. We excluded articles not aligning with our objectives.

Results: Among five fungal cases, four were C. albicans infections. Two patients presented with pain/fever in the vertebra column. All were initially treated as having bacterial spondylodiscitis. Half of the patients had positive blood cultures and all had positive biopsies taken. The two remaining patients had experienced candidemia within one year prior to being diagnosed with spondylodiscitis. All were initially treated with fluconazole with a median duration of 9 months (range 6-12 months). The median time to diagnosis was 27 days (range 23-35 days). Two patients died during treatment. The median follow-up was 7 months (range 6-8 months). Thirteen studies were included in the literature review.

Conclusion: The study described the characteristics, treatment and outcome of C. albicans spondylodiscitis patients in Southern Denmark. Noting prior candidemia episodes can improve early identification and outcomes. Furthermore, our patients exhibit clinical similarities to those in the literature review.

Background and objectives: Malnutrition is associated with prognosis in several heart diseases, but there is little information in patients with infective endocarditis (IE). Our objective was to assess the influence of body mass index (BMI) on the prognosis of IE.

Methods: National registry of patients with definite or probable IE from 2008 to 2021, comparing in-hospital and 1-year mortality according to BMI.

Results: From 3645 patients, 91 (2.5%) were underweight, 1432 (39.3%) had normal weight, 1503 (41.2%) were overweight, and 619 (17.0%) had obesity. The median age was lowest in the underweight group (51 vs. >66 years in the other groups, p < 0.001). Patients with underweight/normal weight had an inferior age-adjusted Charlson comorbidity score than those with overweight/obesity (4 vs. 5, p < 0.001). Tricuspid IE was common in patients with underweight (15.4%), while in other groups its prevalence was <6%, p < 0.001. In-hospital and 1-year mortality were respectively: underweight (26.4% and 34.1%), normal weight (19.9% and 25.8%), overweight (22.4% and 27.8%), and obesity (27.8% and 32.5%), both p values ≤0.01. In multivariate analysis, underweight showed a trend for an association with in-hospital mortality (odds ratio 1.67; 95% confidence interval 0.93-3.01 p = 0.09) and a significant association with 1-year mortality (hazard ratio 1.94; 95% confidence interval 1.14-3.31; p = 0.015).

Conclusions: The prognosis of IE in patients with underweight and obesity is worse than in those with normal weight or overweight, and low weight is an independent predictor of 1-year mortality.

Background: The genus Providencia is increasingly being recognized as an important human pathogen. Previously a member of the family Enterobacteriaceae but now reclassified into the family Morganellaceae along with Morganella and Proteus, the phylogenetic depth of this clade has expanded from 3 species in its inception to 12 as of 2025. Recent clinical and epidemiologic data provide convincing evidence that P. alcalifaciens causes gastroenteritis and there is also increasing recognition of carbapenem-resistant strains of P. stuartii and P. rettgeri causing serious infections in hospital settings.

Objective and methods: Since 2000, no comprehensive review of this genus has been published detailing taxonomic changes, ecological associations, emerging disease trends, pathogenicity and diagnostic modalities useful in detecting and typing providenciae. The objective of this article is to provide a current review and update of recent publications (PubMed, ScienceDirect, Google Scholar, Scopus^®) post-2000 and to summarize results and conclusions to date on this increasingly important genus.

Results: Many reports have now been published describing human cases of enteritis and major outbreaks of gastroenteritis attributed to P. alcalifaciens and supported by multiple epidemiologic lines of evidence including typing methods (serology, molecular), in vivo immune responses, and case-controlled investigations. Similar disease syndromes have also been reported in dogs and pigs with one national canine outbreak of haemorrhagic diarrhoea reported from Norway in 2021. In addition, increasing drug resistance has been noted in both P. stuartii and P. rettgeri leading to the worldwide discovery of multi-, extensive-, and pan-resistant isolates causing disease which presents diagnostic issues in the laboratory and therapeutic challenges.

Conclusion: The analysis reveals that providenciae are increasingly being implicated as important causes of intestinal and systemic disease. This is supported by a ten-fold increase in the number of Providencia studies listed in PubMed between 2000 and 2024. Methods need to be developed in the microbiology laboratory to recognize "pathogenic" strains of P. alcalifaciens that produce enteritis from commensal isolates. Emerging antimicrobial resistance needs to be detected early, monitored, and controlled to avoid further dissemination. New infection control prevention procedures need to be advanced and assessed for usefulness in medical care facilities.

Background: Pseudomonas aeruginosa with difficult-to-treat resistance is a clinical burden. Ceftolozane/tazobactam is recommended for difficult-to-treat P. aeruginosa although cefiderocol represents an option due to its in vitro potency against isolates with ceftolozane/tazobactam-resistance. Head-to-head data assessing these compounds against difficult-to-treat P. aeruginosa are lacking.

Objectives: To assess the efficacy and resistance development of cefiderocol and ceftolozane/tazobactam in a 72-h murine thigh infection model against five clinical difficult-to-treat P. aeruginosa isolates susceptible for both agents and previously developed resistance to ceftolozane/tazobactam in patients.

Methods: Human-simulating regimens of ceftolozane/tazobactam (2/1 g IV q8h) and cefiderocol (2 g IV q8h) were utilized. Efficacy was assessed as the change in bacterial density from starting inoculum and compared to translational endpoints of 1- and 2-log₁₀-kill. Development of resistance was defined as a post-exposure MIC increase greater than 4-fold dilutions.

Results: Cefiderocol reached the 24h 1-log₁₀-kill endpoint in all isolates; however, ceftolozane/tazobactam reached same endpoint in 3/5 isolates. Cefiderocol reached 2-log₁₀-kill in all isolates by 48 h. Conversely, ceftolozane/tazobactam achieved same endpoint in four isolates by 72 h. In the cefiderocol and ceftolozane/tazobactam-treated groups 17% and 8% of the cultures displayed bacterial eradication after exposure to the human-simulating regimens which hinder MIC testing for those samples. Resistance was not detected for either antibiotic postexposure.

Conclusion: Despite susceptibility to both cefiderocol and ceftolozane/tazobactam, cefiderocol provided a more rapid kill profile and achieved a greater magnitude of bactericidal activity relative to ceftolozane/tazobactam. While frank resistance did not develop to either compound, differences in the rate and extent of kill were observed.