Infectious diseases (London, England)最新文献

Background: Despite recommendations by EU, surveillance of Lyme neuroborreliosis (LNB) is still not fully implemented in all member states, Sweden being one of them. Laboratory-based notifications on positive Borrelia antibody index (AI) in paired cerebrospinal fluid-serum samples alone have been suggested for surveillance of LNB.

Objectives: We aim to describe the epidemiology of Lyme borreliosis (LB) and LNB in Southern Sweden and assess if laboratory-based surveillance of LNB alone risks to underestimate the incidence in different populations.

Methods: Using register data, we categorized cases from Region Skåne County during 2009-2022 into four groups: A) cases with positive Borrelia AI, and data on ICD-10 codes given to them; B) cases with ICD-10 code indicating LNB but without positive Borrelia AI; C) cases with Lyme arthritis; and D) other disease manifestations of LB, mainly erythema migrans.

Results: Mean annual incidence for laboratory confirmed LNB (group A) was 3.2/100,000 inhabitants compared to 2.2/100,000 for cases with LNB diagnosis code but without positive Borrelia AI. Highest incidence in both these groups was noted among children 0-9 years old. Among cases in group B, 47% had a diagnosis code indicating facial nerve disorder, compared to19% in group A. For patients in group D, the mean annual incidence was 282/100,000 and increasing.

Conclusion: A considerable number of patients received a LNB diagnosis code without laboratory confirmation. Children and those with facial nerve disorder as LNB manifestation are at risk to be underreported if surveillance of LNB is based on positive Borrelia AI alone.

Background: Sepsis frequently occurs in hospitalised patients with cirrhosis. Among this cohort, meningoencephalitis is likely underdiagnosed, and Cryptococcus neoformans may be a common pathogen.

Objectives: Our study aims to (1) understand the epidemiology and mortality of meningoencephalitis in patients with cirrhosis, (2) identify those at risk for cryptococcal meningitis, and (3) assess the safety of lumbar puncture (LP).

Methods: The National Inpatient Sample was screened from 2016 to 2019 to identify hospital stays during which patients with cirrhosis underwent LP. We characterised the demographics, clinical data, and outcomes of those with and without meningoencephalitis. We then used logistic regression models to identify clinical factors associated with cryptococcal meningitis and described the incidence of LP-related complications.

Results: Among 3,435 hospitalisations, meningoencephalitis occurred in 274 (8%). Of all pathogens, Cryptococcus neoformans was the most common (19%) and most deadly (33% mortality; adjusted odds ratio [aOR] 2.31, 95% confidence interval [CI] 1.12-4.74; p = 0.02). Ascites was the only risk factor associated with cryptococcal meningitis (aOR 2.86, 95% CI 1.68-4.87; p < 0.001). LP-related complications were rare (<1%).

Conclusions: Cryptococcal meningitis is a common and morbid cause of meningoencephalitis among hospitalised patients with cirrhosis. LP is safe and should be considered in those with clinical features of infection without a clear source who fail to improve after standard therapy. However, the role of broader screening strategies among patients with cirrhosis remains uncertain, and further research is needed to refine diagnostic approaches for invasive fungal infections, including cryptococcal meningitis.

Background: While patients with post-COVID syndrome (PCS) suffer from cognitive deficits few studies directly compare patients with PCS to subjects recovered after an infection with the 'Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)'.

Objectives: To investigate cognitive performance adjusting for age, increasing body-mass-index (BMI), smoking, years of education, gender and hospitalisation while infected in patients with PCS compared to controls fully recovered. Secondly, to stratify cognitive performance based on the SARS-CoV-2 virus strain (variant of concern 'VOC') causing the infection. Thirdly, to assess whether patients with PCS have increased levels of psychological distress and affected hand grip strength as both are associated with cognitive performance.

Methods: A Danish-Swedish case-control study we recruited adult patients (18-75 years) with PCS from long-COVID outpatient clinics in Region Zealand Denmark and Skåne County Sweden. Participants had confirmed SARS-CoV-2 infection >12 weeks prior to inclusion and healthy control subjects had recovered completely. All study participants were exposed to cognitive tests, Kessler's psychological distress scale (K10) and tested with a hand-dynamometer.

Results: Recruiting 181 cases and 155 control subjects, patients with PCS had reduced cognitive performance scores on all domains though hardly clinically significant. Reduced processing speed was impacted the most with patients infected early in the pandemic exhibiting greater deficits.

Conclusion: PCS was associated with reduced cognitive processing speed compared to fully recovered controls with those infected early in the pandemic having greater deficits. Psychological distress and hand grip strength were affected in patients with PCS, but not decisively associated with cognitive performance.

Background: The surface antigen of hepatitis B virus (HBsAg) is present on viral particles (VP) and subviral particles (SVP) and is produced from both covalently closed circular DNA (cccDNA) and HBV DNA integrated into human chromosomes.

Objective: To calculate the contribution of VP and SVP to HBsAg levels in serum, and study to what extent the source of HBsAg is cccDNA or integrated HBV DNA.

Method: Analysis of HBV DNA and HBsAg levels from subjects with chronic HBV infection and after initiation or cessation of antiviral treatment.

Results: In serum samples from 800 individuals with chronic HBV infection and no antiviral treatment, the ratio between SVP and VP was > 100 million among HBe-antigen-negative subjects with low viral load. During initiation of nucleos(t)ide analogue (NA) treatment of 12 patients, the decline of HBsAg in serum was marginal or absent despite marked second phase reductions of HBV DNA, a proxy for cccDNA decline. After discontinuation of NA treatment, no increase in HBsAg levels was observed until HBV DNA had reached very high levels.

Conclusions: Viral particles do not significantly contribute to HBsAg levels in serum and in HBeAg-negative patients, and the VP/SVP ratio is much lower than previously described. The contribution from cccDNA to HBsAg levels seems to be significant only when the HBV DNA serum levels are very high and reflect a cccDNA content in the liver that produces HBsAg in amounts that equal or are greater than from integrated HBV DNA.

Background: Ceftolozane/tazobactam (C/T) in combination with metronidazole is an active antimicrobial therapy used to treat complicated intra-abdominal infections (cIAIs).

Methods: A comparison of the clinical efficacy of C/T plus metronidazole vs. meropenem for the treatment of cIAIs using pooled data from four phase 3 clinical studies (CXA-cIAI-10-08, CXA-cIAI-10-09, NCT02739997 and NCT03830333).

Results: In total, 1,361 patients (C/T plus metronidazole, n = 721; meropenem, n = 640) were included in the pooled analysis. Clinical response rates at the test of cure (TOC) visit in the intention-to-treat (ITT) and clinically evaluable populations were 84.3% (608/721) and 86.9% (556/640) as well as 93.4% (534/572) and 93.8% (483/515), and at the end of treatment visits the rates were 90.6% (653/721) and 91.9% (588/640) as well as 96.5% (552/572) and 96.6% (499/515) for C/T plus metronidazole and meropenem, respectively. Microbiological response rates at the TOC visits in the modified ITT population were 85.3% (440/516) and 89.3% (442/495), and in the extended microbiological evaluable population 93.7% (399/426) and 94.3% (394/418) for C/T plus metronidazole and meropenem, respectively. Adverse events occurred in 341/716 (47.6%) and 280/631 (44.4%) patients treated with C/T plus metronidazole and meropenem, respectively. The most common adverse events across treatment groups were diarrhoea, nausea, pyrexia and insomnia. No new serious safety findings were identified.

Conclusions: The efficacy of C/T plus metronidazole was comparable with meropenem even for cIAIs and C/T plus metronidazole might be an alternative treatment option for cIAI.

Background: The combination of antivirals and monoclonal antibodies (mAbs) in the first phase of COVID-19 has demonstrated to reduce time to viral clearance, but the superiority of combination compared to antiviral monotherapy is still debated.

Research design and methods: In an observational, prospective study, we enrolled immunocompromised outpatients with mild-to-moderate COVID-19 treated with one antiviral monotherapy within 7 days from symptoms onset, with or without sotrovimab from January 1, 2024 to October 31, 2024, and we compared them to an identical cohort of patients treated with a combination of one antiviral and sotrovimab, from May 1, 2023 to December 30, 2023. 1st of May 2023 and 31st of October 2024. Sotrovimab administered until the end of October 2023 was considered to be presumably effective against the circulating viral variants, based on virological reports.

Results: We enrolled considered 98 patients treated with nirmatrelvir/ritonavir or remdesivir. Sotrovimab was co-administered in 50/98 cases. All the patients cleared SARS-CoV-2 infection within a median of 17 (IQR 10-22) days. At the multivariate Cox regression analysis, therapy administration within 3 days from symptoms' onset (aHR 1.68; p = 0.031) and presumed sotrovimab effectiveness (aHR 1.75; p = 0.02) were found to be independent factors associated with for shorter time to viral clearance.

Conclusions: The timing of administration of early antiviral therapy is crucial to reduce SARS-CoV-2 infection duration in immunocompromised patients and the combination with a mAb is associated with earlier viral clearance, as long asmAb is chosen among those effective against circulating variants.

Background: Tuberculosis (TB) remains a major public health issue in Bengaluru, India. This study analyzes TB trends, treatment outcomes, and the impact of COVID-19 on TB incidence from 2017 to 2023.

Methods: Logistic regression analysis was used to identify factors influencing TB treatment outcomes. An Interrupted Time Series (ITS) analysis using an ARIMA (AutoRegressive Integrated Moving Average) model was used to assess the impact of COVID-19 on TB incidence.

Results: Among 71,883 TB cases, age ≥65 years had increased the risk of unsuccessful outcomes for pulmonary TB (PTB) (adjusted odds ratio [aOR] 2.54; 95% confidence interval [CI], 2.24-2.89) and extrapulmonary TB (EPTB) (aOR 3.72; CI, 3.06-4.52). Females had lower odds than males in PTB (aOR 0.72; CI, 0.67-0.78) and EPTB (aOR 0.77; CI, 0.68-0.86). Diabetics had lowered risk for PTB (aOR 0.62; CI, 0.57-0.68) but increased risk for EPTB (aOR 1.44; CI, 1.24-1.67). HIV cases had increased risk in PTB (aOR 1.96; CI, 1.67-2.31) and EPTB (aOR 2.88; CI, 2.32-3.57). Interaction analysis in PTB showed diabetics with ages 35-44 and 45-54 was associated with lower risk (aOR 0.66; CI, 0.44-0.99; aOR 0.67; CI, 0.46-0.99). ITS analysis showed a 24.3% average decline in TB notifications in 2020, reaching a maximum decline of 40.5% in April.

Conclusion: This study highlights factors affecting TB treatment outcomes and the significant impact of COVID-19 on TB trends in Bengaluru, providing insights to improve TB control and mitigate future pandemic impacts.

Objectives: This study aims to compare risk factors and mortality of candidemia by Candida auris versus Candida non-auris in intensive care units (ICU).

Methods: A total of 437 ICU patients who developed candidemia (90 C. auris, 143 C. albicans, 204 other Candida spp.) in 2021-2023 were included. The risk factors in candidemia caused by C. auris, C. albicans and other Candida spp. were compared. Factors associated with 30-day mortality in C. auris candidemia were explored.

Results: Compared to the C. albicans group, the C. auris group had more frequent ceftazidime avibactam use (OR:6.72, 95%CI: 1.29-34.98, p = 0.024) and tracheostomy (OR:4.13, 95%CI: 1.70-10.02, p = 0.002), longer colistin (OR:1.07, 95%CI: 1.01-1.13, p = 0.021) and urinary catheter use (OR:1.02, 95%CI: 1.01-1.03, p = 0.023). Compared to the other Candida spp. group, colistin use (OR:2.79, 95%CI: 1.61-4.87, p < 0.001), chronic obstructive pulmonary disease (OR:2.02, 95%CI: 1.05-3.90, p = 0.036) and concurrent bacteraemia (OR:1.92, 95%CI: 1.06-3.48, p = 0.030) were more frequent in the C. auris group. Rate of 30-day mortality was lower in C. auris patients (63.3%) compared to the C. albicans (82.5%) and other Candida spp. (75.5%) groups. While the 30-day mortality rate was higher in C. auris patients who received vasopressor therapy (OR:3.12, 95%CI: 1.78-5.47, p < 0.001) and had high lactate levels (OR:1.41, 95%CI: 1.00-1.99, p = 0.047) and low platelet counts (OR:1.00, 95%CI: 0.99-1.00, p = 0.003) on the first day of candidemia, it was lower in patients with microbiologic response (OR:0.03, 95%CI: 0.01-0.09, p < 0.001).

Conclusion: The necessity of broad-spectrum antibiotics and indwelling catheters should be routinely reassessed to reduce C. auris candidemia. Lower mortality was linked to microbiologic response; thus, fungal eradication should be prioritised in clinical practice.