Open Forum Infectious Diseases最新文献

Vancomycin-resistant Enterococcus faecium (VREfm) has become a significant nosocomial pathogen due to its potential to cause outbreaks. Whole-genome sequencing (WGS) is considered the reference method for determining genomic relatedness among outbreak strains, but its routine use in clinical microbiology laboratories remains challenging. Consequently, faster and simpler typing methods are needed. Fourier transform infrared spectroscopy (FTIR) captures the unique infrared fingerprint of each isolate, enabling the comparison of spectral profiles to infer genomic relatedness. In this study, we evaluated the performance of FTIR for identifying genomic clusters of VREfm in a tertiary hospital, in comparison with three WGS-based methods: core-genome multilocus sequence typing (cgMLST), core-genome single nucleotide polymorphism analysis (cgSNP), and split k-mer analysis (SKA). A total of 87 VREfm isolates, collected between April 2020 and October 2023, were typed using both FTIR and WGS. Among these, 56 were associated with three outbreaks in the surgery, nephrology, and oncohematology units, according to conventional epidemiology. Concordance between typing methods was assessed using the Adjusted Rand index (AR) and Adjusted Wallace coefficient (AW). All three WGS-based methods yielded similar clustering results and revealed one monoclonal and two polyclonal outbreaks. Using cgMLST as the reference, an optimal FTIR cutoff range of 0.210-0.227 was determined. FTIR clustering results showed strong concordance with WGS-based methods; however, concordance with SKA was slightly lower. These findings suggest that FTIR provides clustering information comparable to WGS-based methods, providing a rapid and practical alternative to support timely infection control measures during VREfm outbreaks.

Background: Cryptococcal meningitis (CM) is a significant cause of morbidity and mortality in individuals with advanced HIV. Ethiopia, with a high HIV burden and significant socioeconomic challenges, has limited data on CM. Understanding clinical practices is crucial to identifying gaps and improving disease management.

Methods: A survey was conducted among health care workers (HCWs), microbiologists, and pharmacists across 9 Ethiopian health facilities from July to November 2024. Eligibility required active involvement in HIV or CM care. Ethics approval and informed consent were secured. Three profession-specific questionnaires were used to assess knowledge of CM care and challenges. Data were analyzed in R, version 4.3.2.

Results: A total of 311 participants were included: HCWs, n = 202; microbiologists, n = 65; and pharmacists, n = 44. Most participants, 188/202 (93.1%) HCWs, 42/44 (95.5%) pharmacists, and 54/65 (83.1%) microbiologists, recognized the need for additional guideline training. Only 59/202 (29%) HCWs reported that screening for cryptococcal antigenemia was always performed. Among antifungals, fluconazole was the most available, with 21/44 (48%) pharmacists and 49/202 (24%) HCWs reporting it as always in stock. Liposomal amphotericin B (L-Amb) was reported as available by only 7/44 (16%) pharmacists and 44/202 (22%) HCWs. The most significant barriers to guideline implementation were insufficient policy support and challenges in integrating guidelines into electronic health records, as reported by 152/202 (75.2%) and 143/202 (70.8%) HCWs, respectively.

Conclusions: There are substantial gaps in CM care, highlighting the importance of improving resource allocation, technical assistance, additional training, and financial support.

Syphilis and hepatitis C virus (HCV) rates have increased among women of childbearing age. Given the potential for vertical transmission of both infections, we examined syphilis and HCV co-infection among pregnant women in West Virginia (2019-2023). Public health surveillance data for syphilis and HCV were cross-referenced to identify co-infections. Of the 161 pregnant women with syphilis, 42.9% had a past or present HCV infection. Compared with those without HCV, a greater proportion of women with past or present HCV self-reported incarceration (21.7% vs 5.4%) and drug use (50.7% vs 15.2%) during the past year. Notably, women with past or present HCV had lower adherence to syphilis treatment (56.5% vs 84.8%) and a higher frequency of reported congenital syphilis outcomes (59.4% vs 28.3%). Findings support the need for integrated care approaches to address overlapping infections and associated social vulnerabilities.

Phase 1 and Phase 2/3 trials (NCT04816643) demonstrated that the mRNA-based coronavirus disease 2019 (COVID-19) vaccine BNT162b2 is tolerable and efficacious in (5-11-year-olds) following two 10 µg doses 21 days apart, and a third 10 µg dose after 6 months. Here, we show that vaccination induces neutralizing antibodies and T-cell immunogenicity in 10-11-year-old participants.

Background: Factors associated with weight change were examined in phase 3 studies in which adults living with HIV-1 continued or switched to doravirine-based antiretroviral regimens.

Methods: Participants were randomized to first-line therapy with doravirine or darunavir/ritonavir, each given with 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) (DRIVE-FORWARD) and to doravirine/lamivudine/tenofovir disoproxil fumarate (TDF) or efavirenz/emtricitabine/TDF (DRIVE-AHEAD); after 96 weeks, participants continued (n = 466) or switched to (n = 423) doravirine for 96-week open-label extensions. In DRIVE-SHIFT, virologically suppressed participants on stable antiretroviral therapy were randomized to switch to doravirine/lamivudine/TDF at day 1 or week 24 through week 144 (n = 535). Generalized logistic models were used to analyze factors associated with weight loss (≥5% decrease), stable weight (<5% change), and weight gain (≥5% increase) after continuation or switch.

Results: Most participants who continued or switched to doravirine also received TDF (>74%) and had stable weight (>57%). Weight loss (odds ratio [OR], 6.14) or stable weight (OR, 2.15) was more common in participants of non-Black versus Black heritage after switching to doravirine. More participants switching from weight-suppressive non-nucleoside reverse transcriptase inhibitors versus protease inhibitors experienced weight gain versus weight loss in DRIVE-SHIFT (OR, 0.41) and weight gain versus stable weight in DRIVE-FORWARD and DRIVE-AHEAD (OR, 0.60). No significant association between weight change and prior NRTI use was observed in DRIVE-SHIFT.

Conclusions: Overall, switching to doravirine was weight neutral, although weight change may differ by demographics and weight-suppressive properties of a prior regimen. More research in historically underrepresented groups may help explain these findings.

Clinicaltrialsgov: NCT02275780, NCT02403674, NCT02397096.

Background: Few studies have investigated the diagnosis and management of pediatric visceral leishmaniasis (VL) in high-income countries.

Methods: All children hospitalized for VL in university hospitals across mainland France between January 2012 and August 2022 were included in this retrospective study.

Results: Sixty-three patients were included with an M/F sex ratio of 1.25 and a median age of 2 years (IQR: 1; 5.4). At least 36 patients had autochthonous VL. The median delay between symptom onset and diagnosis was 20 days (IQR: 11.7; 35.2) [1-193]. The most common symptoms were fever (92%) and splenomegaly (78%). Biological findings included inflammatory syndrome (90%), pancytopenia (79%), and hepatic cytolysis (52%). Twenty-four children (44%) presented hemophagocytic lymphohistiocytosis (HLH). Bone marrow smears, bone marrow real-time PCR (qPCR), and blood qPCR were positive for VL in 64%, 90%, and 96% of the tested patients, respectively. Positivity reached 100% in patients who underwent combined blood and bone marrow PCR. All the patients were treated with liposomal amphotericin B (chemical name, (1R,3S,5R,6R,9R,11R,15S,16R,17R,18S,19E,21E,23E,25E,27E,29E,31E,33R,35S,36R,37S)-33-[(2R,3S,4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid;2-aminoguanidine). Ten different regimens were used, ranging from 18 to 30 mg/kg cumulative doses given from 2 to 8 days. The median follow-up duration was 2.8 months. Four patients (6.3%) relapsed, one of whom was not retreated. All the children recovered.

Conclusions: Pediatric VL remains rare in France, with long diagnostic delays and a high frequency of HLH. The combination of blood and bone marrow PCR optimizes the diagnosis. Standardization of therapeutic regimens and follow-up is necessary.

Background: Older people living with HIV (PWH) are disproportionately affected by an increasing burden of comorbidities. There are few clinical trials of switching antiretrovirals in this population, particularly in Africa.

Methods: In this open-label randomized trial, virally suppressed PWH aged ≥60 years were randomized 1:1 to switch to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or to continue their current antiretroviral regimen (CAR) at two sites in Kenya. Participants had bone mineral density (BMD) measurement at baseline, and at weeks 24 and 48. Calcium and vitamin D supplementation was provided to all participants beginning partway through the study because of high rates of osteoporosis identified at baseline. The primary endpoints were proportion of participants with plasma HIV-1 RNA of ≥50 copies/mL at week 48 using the US Food and Drug Administration snapshot algorithm, a non-inferiority margin of 4%, and the percentage change in the lumbar spine BMD at week 48. We report the primary efficacy, BMD and safety analysis at week 48. The study is continuing to week 96.

Results: Between March and July 2022, we enrolled 520 participants with 260 randomized to switch to B/F/TAF and 260 to continue CAR and were included in intention-to-treat analysis. At week 48, 1.9% (5/260) of participants had HIV-1 RNA ≥ 50 copies/mL in the B/F/TAF arm and 2.7% (7/260) in the CAR arm (treatment difference [95% CI], -0.8% [-3.4 to 1.8]), indicating non-inferiority. Change in lumbar spine BMD at week 48 was +2.18% in the B/F/TAF arm and 0.68% in the CAR arm (difference 1.51, CI .27-2.76, P .017). Treatment-related grade 3 or 4 adverse events were similar across arms (16.9% on B/F/TAF; 14.2% on CAR). Fifteen participants had grade 3 or 4 AEs leading to study drug discontinuation, all in the CAR arm due to declining kidney function. More participants on B/F/TAF developed incident dyslipidemia compared with participants on CAR (23% on B/F/TAF; 14% on CAR; P .015).

Conclusions: Switch to B/F/TAF was non-inferior to CAR and safe in an African population aged ≥60 years.

Background: A deficient vitamin D status is linked to increased risk of community-acquired pneumonia (CAP) and both short- and long-term mortality. Given small sizes of previous studies and lack of adjustment for key confounders, we aimed to investigate the association between vitamin D status (sufficient, insufficiency, or deficiency) and mortality risk in adults hospitalized with CAP.

Methods: This study, nested within the Surviving Pneumonia Study at Copenhagen University Hospital-North Zealand, Denmark, included adults hospitalized with CAP between 2019 and 2022. Vitamin D status was assessed using serum 25(OH)D concentrations, categorizing participants as sufficient (≥50 nmol/L), insufficient (25-<50 nmol/L), or deficient (<25 nmol/L). Logistic regression was used to assess mortality risk. Covariates included age, sex, Charlson comorbidity index, CURB-65, smoking history, and BMI.

Results: Among 514 participants, 29 (5.6%) and 130 (25.3%) had deficient and insufficient vitamin D status, respectively. Participants with deficient vitamin D status were younger, and more than 50% were current smokers. Vitamin D deficiency was associated with higher 90-day (OR: 3.50, 95% CI 1.01; 12.21) and 180-day (OR: 3.27, 95% CI 1.04; 10.25) mortality risk compared with participants with sufficient vitamin D status, while no difference was observed between the sufficient and insufficient group. No differences were observed for in-hospital or 30-day mortality.

Conclusions: Participants with deficient vitamin D status were younger and faced higher mortality risk despite milder disease at admission. Given that vitamin D deficiency may relate to poorer health habits and low levels of other micronutrients, trials on tailored micronutrient supplementation during acute conditions like CAP could be considered.

In this ongoing, open-label, phase 3b/4 study, JN.1- and KP.2-encoding monovalent mRNA-1273 vaccines elicited robust neutralization of vaccine-matched variants (JN.1, KP.2) and cross-neutralized JN.1 subvariants circulating during the study (September 2024-November 2024; KP.3.1.1, XEC, LP.8.1) in vaccinated adults, showing reduced cross-neutralization against all subvariants tested. No safety concerns were identified.