Journal of Infection最新文献

Introduction: The increase in the population of immunocompromised patients due to advances in management of end-stage diseases and transplants poses challenges in treating infections caused by multi-drug resistant (MDR) pathogens. Cefiderocol (FDC), a siderophore cephalosporin, has shown efficacy against carbapenem-resistant Gram-negative bacteria.

Methods: This retrospective multicentre study investigated the real-world use of FDC in 114 immunocompromised adults treated for MDR infections in 12 French hospitals (June 2020-November 2023). Clinical and microbiological outcomes, including infection cure, relapse, as well as mortality, and resistance acquisition, were assessed at days 28 and 90. Antibiotic prescription compliance with current guidelines was investigated.

Results: At day 28, clinical success was achieved in 53.3% of cases, and overall mortality was 37.7%, consistent with other studies (33-37%). Infection-related mortality accounted for 25.4%. Relapse occurred in 17.5% of patients by day 28, rising by an additional 9.8% among survivors by day 90. Resistance acquisition was observed in two cases at day 28 (Pseudomonas aeruginosa and Stenotrophomonas maltophilia) and in three additional cases by day 90. FDC was used as monotherapy in 49.1% of cases, with a median treatment duration of 10 days. Nearly 25% of strains collected in FDC-treated patients were susceptible to best-practice alternatives.

Conclusion: These findings highlight FDC's utility in difficult-to-treat infections, particularly S. maltophilia, but the high relapse rate and resistance acquisition underscore the need for careful monitoring, adherence to guidelines, and reconsideration of empirical use to prevent resistance and improve outcomes in fragile populations.

Objectives: We aimed to evaluate the adaptive immune responses cross-recognition of the hypermutated SARS-CoV-2 BA.2.86 variant and identify the determinants influencing this recognition.

Methods: We measured BA.2.86 neutralizing antibodies and T-cell responses cross-reactivity in previously exposed participants. We investigated clinical-demographic factors and used a novel in silico analysis to assess viral genetic determinants affecting T-cell responses.

Results: Despite notable escape from neutralizing antibodies, T-cell responses remained generally preserved, albeit with a significant but small loss in T-cell cross-recognition (7.5%, 14.2%, and 10.8% average loss for IFN-γ, IL-2, and IFN-γ + IL-2, respectively, p<0.05). This is consistent with the prediction of 6 out of 10 immunodominant T-cell epitopes (TCEs) altered by BA.2.86 mutations to have reduced peptide presentation. This effect is expected to be mitigated by total TCEs across the genome. Remarkably, T-cell responses and cross-recognition were 3.5 (IFN-γ), 2 (IL-2) and 2.4 (IFN-γ + IL-2) times higher when first induced by infection rather than by vaccination three years earlier, by increasing number of infections, and by ancestral/Delta than Omicron infections.

Conclusions: Our findings underscore the critical role and factors influencing T-cell immunity against evolving SARS-CoV-2 variants, such as first antigen encounter (vaccination or infection), as it is essential for developing effective control strategies.

Background: Patients with Gram-negative bloodstream infections are at risk of serious adverse outcomes without active treatment, but identifying who has antimicrobial resistance (AMR) to target empirical treatment is challenging.

Methods: We used XGBoost machine learning models to predict antimicrobial resistance to seven antibiotics in patients with Enterobacterales bloodstream infection. Models were trained using hospital and community data from Oxfordshire, UK, for patients with positive blood cultures between 01-January-2017 and 31-December-2021. Model performance was evaluated by comparing predictions to final microbiology results in test datasets from 01-January-2022 to 31-December-2023 and to clinicians' prescribing.

Findings: 4709 infection episodes were used for model training and evaluation; antibiotic resistance rates ranged from 7-67%. In held-out test data, resistance prediction performance was similar for the seven antibiotics (AUCs 0.680 [95%CI 0.641-0.720] to 0.737 [0.674-0.797]). Performance improved for most antibiotics when species identifications (available ∼24 h later) were included as model inputs (AUCs 0.723 [0.652-0.791] to 0.827 [0.797-0.857]). In patients treated with a beta-lactam, clinician prescribing led to 70% receiving an active beta-lactam: 44% were over-treated (broader spectrum treatment than needed), 26% optimally-treated (narrowest spectrum active agent), and 30% under-treated (inactive beta-lactam). Model predictions without species data could have led to 79% of patients receiving an active beta-lactam: 45% over-treated, 34% optimally-treated, and 21% under-treated.

Conclusions: Predicting AMR in bloodstream infections is challenging for both clinicians and models. Despite modest performance, machine learning models could still increase the proportion of patients receiving active empirical treatment by up to 9% over current clinical practice in an environment prioritising antimicrobial stewardship.

Background: Shifts in dietary patterns during lifestyle transitions are integral components of the dynamic interactions between humans and their environments. Investigating the link between dietary diversity, the composition of the human lipidome and infection is key to understanding the interplay between diet and susceptibility to pathogens.

Methods: Here we address this question by performing a comparative study of two ethnic groups with divergent dietary patterns: Fulani, who are nomad pastoralists with a dairy-centric diet, and Mossi, who are farmers with a plant-based diet. We generate 196 paired global lipidomes (927 lipid molecules) from both groups before and during natural Plasmodium falciparum infection.

Results: Our analysis revealed 211 significantly differentially abundant lipid molecules between the two ethnic groups in both infection states. We show that ethnicity has a greater impact on the lipidome of these children than do P. falciparum infection and report inter-ethnic differences that impact pathogenesis. We highlight elevated levels of pentadecanoic acid (C15:0)-containing phospholipids in Fulani and experimentally demonstrate the suppressive effects of lysophosphatidylcholine LysoPC (15:0) on P. falciparum gametocyte production.

Conclusion: These findings link the Fulani's dairy-centric diet and lower P. falciparum gametocyte densities reported in this group and underscore the intricate links between dietary lipids and the host response to infection.

Background: Disease severity and pregnancy outcomes following SARS-CoV-2 reinfections in pregnancy are not well understood.

Methods: We linked women aged 18 to 50 years testing positive in the community for COVID-19 between April 2021 and March 2022 to hospital, vaccine and maternal services databases. We compared hospital and intensive care unit (ICU) admission rates following infection and reinfection in pregnant and non-pregnant women, and low birthweight, prematurity and stillbirth in women infected and reinfected during pregnancy.

Results: We identified 68,842 pregnant and 3,915,069 infected non-pregnant women. Hospital admission after SARS-CoV-2 reinfection was more common in pregnancy, especially during the third trimester (aOR= 18.56; 95% CI: 9.46 - 36.42) and was similar following reinfection or primary infection in pregnancy (aOR= 0.82; 95% CI: 0.50 - 1.33). All ICU admissions (n=49) in pregnancy occurred after primary infection with delta. There was no notable difference in adverse pregnancy outcomes after primary infection or reinfection with SARS-CoV-2 during pregnancy.

Conclusion: Pregnant women remain at higher risk of more severe disease during reinfection compared to non-pregnant women yet; hospitalisation and ICU admissions risk were low during the omicron period. The virulence of circulating variants needs to be assessed to guide maternal COVID-19 vaccination programmes against.

Background: Healthcare workers were at a high risk of infection early in the SARS-CoV-2 pandemic. It is uncertain to what extent occupational, household and community factors contributed, and how this changed over time. We aimed to characterise the risk factors for infection over four successive waves of the pandemic in a large, UK healthcare worker cohort (SIREN).

Methods: Participants underwent fortnightly SARS-CoV-2 PCR testing and symptom/exposure survey. Attack rates and adjusted OR of infection were calculated according to participant characteristics and exposures for each wave between 1^st October 2020 and 30^th August 2022.

Findings: 19,427 participants were included in the second wave, 20,260 in the third, 11,937 in the fourth, and 6,503 in the fifth. The attack rates of infection were 9.1% (alpha), 6.6% (delta), 36.6% (omicron BA.1/2) and 15.9% (omicron BA.4/5) respectively. Occupational risk factors were only apparent in the second wave, during which significant social distancing measures were in place. These were identified as working as a healthcare assistant, nurse or bedside therapist, and working on an inpatient ward. Occupational exposure requiring personal protective equipment was also a risk. In subsequent waves, without social restrictions, occupational characteristics were not risk factors. Instead, living with others compared to living alone was a risk, particularly children. During the third wave (winter 2021-2022), having a colleague with COVID-19 was identified as a risk for the first time.

Interpretation: Our findings highlight clinical areas and occupational groups in which there may be scope to prevent healthcare-associated infections, particularly during winter pressures. Prospective studies targeting these are essential to establish which interventions are most effective. This study also underscores the importance of community circulation and exposures when considering healthcare workforce protection.

Background: Metagenomic next-generation sequencing (mNGS) is an effective method for detecting pathogenic pathogens of bloodstream infection (BSI). However, there is no consensus on whether the use of antibiotics affects the diagnostic performance of mNGS. We conducted a prospective clinical study aiming to evaluate the effect of antimicrobial treatment on mNGS.

Methods: Blood samples were collected for mNGS testing within 24 h of culture-confirmed with BSI, with re-examination conducted every 2-3 days.

Results: A total of 38 patients with BSI were enrolled. The mNGS positive (mNGS-pos) rate declined sharply after the use of antibiotics, with only 17 (44.78%) patients remaining mNGS-pos while the rest were mNGS negative (mNGS-neg). The median duration of pathogen identification was significantly longer for mNGS compared to blood culture (BC) (4 days vs 1 days; P < 0.0001). A positivity duration of ≥ 3 days was an independent risk factor of septic shock (OR, 20.671; 95% CI, 1.958-218.190; P = 0.012). Patients with mNGS-pos and mNGS-neg differed by the median duration of fever (6 days vs 3 days; P = 0.038), rates of drug resistance (35.3% vs 4.8%; P = 0.017), rates of septic shock (47.1% vs 14.3%; P = 0.029), and 28-day mortality (29.4% vs 4.8%; P = 0.041).

Conclusions: The antimicrobial treatment will greatly reduce the positive rate of mNGS. The duration of mNGS is significantly longer than that of BC. The prolonged duration of mNGS suggests an increased risk of septic shock and could be identified as a high-risk factor of adverse infection outcome, requiring more aggressive anti-infective treatment measures.

Objective: To describe the clinical features and outcome of brain abscess since introduction of computerized tomography and magnetic resonance imaging.

Methods: MEDLINE and Embase were searched using "brain abscess" or "cerebral abscess" from 1970 through 2023 and analyses restricted to study populations hospitalized after 1980. Single-variable meta-analyses were done using a random-effects model.

Results: A total of 21,840 patients from 209 studies were included. The mean age was 34 years (95% confidence interval [CI] 30-38) and 11,817/17,406 (66%, 95% CI 64-67) were male. The aetiologies were consistent across time and continents with Streptococcus spp. 2,064/6,393 (32%, 95% CI 28-36), Staphylococcus spp. 1,061/6,393 (14%, 95% CI 12-16), and Gram-negative enteric bacteria 696/6,393 (9%, 95% CI 7-11) as the most common. Predisposing conditions included otitis media/mastoiditis 1,909/6,433 (27%, 95% CI 22-33), immunocompromise 1,022/4,652 (19%, 95% CI 14-24), sinusitis 565/3,725 (16%, 95% CI 12-20), and neurosurgery 745/4,927 (16%, 95% CI 12-20). The case-fatality was 2,444/18,991 (12%, 95% CI 11-14) and good recovery was found in 3,419/5,409 (63%, 95% CI 58-68).

Conclusions and relevance: Brain abscess remains a disease predominantly occurring in men and was caused by contiguous or distant infections. Case fatality and outcome have not improved during recent decades.