Open Forum Infectious Diseases最新文献

Implementation of a long-acting injectable antiretroviral treatment program requires substantial multidisciplinary effort, particularly for program coordination, coverage/billing, and patient support/retention. As our program scaled to 113 patients over 2.5 years, a total of 2.25 full-time equivalents were required. Despite operational demands, clinical outcomes were favorable, supporting real-world feasibility and scalability.

Background: Respiratory syncytial virus (RSV) and SARS-CoV-2 can cause acute respiratory failure in children. We compared characteristics and outcomes of children aged <2 years with respiratory failure from infection with RSV, SARS-CoV-2, or both viruses.

Methods: We used data from a US pediatric respiratory virus hospitalization surveillance network including children with ICU admission for acute respiratory failure (receiving high-flow oxygen or mechanical ventilation) with RSV and/or SARS-CoV-2 during November 2023-March 2024. Demographic, clinical characteristics, and hospitalization outcomes were stratified by a positive test for RSV, SARS-CoV-2, or both viruses, and compared using chi-squared or Kruskal-Wallis tests. Multivariable analyses assessed independent associations between outcomes and infection.

Results: Overall, 1406 children were included: 1253 (89.1%) for RSV, 105 (7.5%) for COVID-19, and 48 (3.4%) with RSV + SARS-CoV-2 detected. Children with RSV or RSV + SARS-CoV-2 had lower median ages (3.9 and 5.4 months, respectively) compared with those with SARS-CoV-2 (8.8 months; P < .001). Twenty percent of children with RSV and 43.8% with COVID-19 had an underlying medical condition. Among infants aged <1 year for whom preterm status was available, 31.5% with RSV and 50% with COVID-19 had either prematurity or a comorbidity. Children with SARS-CoV-2 were more likely to require invasive mechanical ventilation, receive vasoactive infusions, and die compared with RSV with and without SARS-CoV-2.

Conclusions: Critically ill children <2 years of age infected with SARS-CoV-2 had more severe illness presentation and outcomes and were older compared with those with RSV and RSV + SARS-CoV-2 codetection. Most children were previously healthy, highlighting the need for prevention measures.

Inpatient infectious disease (ID) consult services have recently been experiencing increased patient volumes due to a variety of factors, including higher patient complexity, increased patient turnover, growing rates of antimicrobial resistant infections, population aging, and ID outbreaks. As a result, increased time and resources have been required to continue to deliver high-quality medical care to patients. At academic teaching hospitals, providing patient care in the context of increased volumes must be balanced with the educational mission for trainees. Rounding is a central component of ID clinical work which brings together patient care and education. In this narrative review, we aim to delineate different rounding styles and summarize the literature on inpatient rounding. We also discuss unique aspects of inpatient ID rounding and consider advantages and disadvantages of different rounding styles with attention to their impact on patient care, education, and workflow.

Background: Outbreaks of zoonotic emerging infectious diseases, including viral hemorrhagic fevers, are increasing in frequency. Clinical detection remains challenging due to the lack of pathognomonic signs or symptoms and limited access to diagnostics. To better understand the prevalence of prior exposure to viral hemorrhagic fever viruses, serum from community participants in rural Liberia was tested for immunoglobulin G antibodies.

Methods: Serum collected from individuals enrolled in the ENABLE study, an observational study of Lassa fever virus incidence and seroprevalence, were analyzed for immunoglobulin G against Ebola virus, Marburg virus, Lassa virus, Rift Valley Fever virus, Crimean-Congo hemorrhagic fever virus, pan-alphavirus, and pan-flavivirus by MAGPIX, a multiplex immune assay. Associations with seropositivity were evaluated using questionnaires that included demographic, animal, and environmental exposure information.

Results: Eighty-eight percent of samples from 456 participants tested positive for ≥1 of the viral antibodies with a majority (63%) having antibodies to ≥2 viruses. Seropositivity was highest for Lassa virus (67%) followed by pan-flavivirus (51%), pan-alphavirus (35%), Crimean-Congo hemorrhagic fever virus (24%), Ebolavirus (13%), Rift Valley Fever virus (9%), and Marburg virus (8%). Older age, sex (variable by pathogen), and exposure to cats and rats were associated with seropositivity.

Conclusions: These findings demonstrate a significant spillover of filoviruses, bunyaviruses, flaviviruses, and alphaviruses in rural Liberia in contrast with an absence of detected outbreaks. These data support the need for enhanced surveillance and understanding of the ecological and behavioral risk factors for zoonotic spillover events, across a spectrum of disease presentation, given their potential and ongoing threat to global public health.

Background: Preexposure prophylaxis (PrEP) to prevent HIV-1 acquisition is a critical component of the strategy to achieve epidemic control and elimination goals. Previous studies assessing PrEP needs have not considered people based on individualized, quantitative risk profiles, potentially overlooking opportunities to increase PrEP use among all individuals vulnerable to acquiring HIV.

Method: We modeled the risk distribution of sexually acquired HIV infection based on patterns of sexual activity among sexually active adults living in the United States. We estimated the population impact of PrEP use assuming "optimal" (PrEP perfectly distributed to those at highest risk) or "suboptimal" (distributed to only 50% of highest-risk individuals) PrEP distribution.

Results: The model predicts that PrEP use by 1 million and 10 million individuals would prevent ∼3400 and 13 600 sexually acquired HIV infections per year, respectively, with optimal distribution, and 2700 and 9100 infections with suboptimal distribution. In addition to men who have sex with men, heterosexual women make up a significant proportion of the optimally targeted population.

Conclusions: Our model provides a framework to estimate the potential population impact of PrEP. While results vary depending on assumptions, our findings strongly suggest that increases in PrEP uptake, substantially beyond current targets, may be required to achieve epidemic elimination goals. Our findings can inform updated assessments of PrEP coverage and provider initiatives at the individual level. Assessment of HIV acquisition risk based on individual behavior rather than risk-group membership indicates the imperative for wider PrEP distribution than currently occurs.

Pharmacokinetic (PK) and pharmacodynamic (PD) variability in special populations can impact antimicrobial efficacy and safety. This review highlights the importance of PK/PD optimization in patients known to have altered PK, including those with obesity, cystic fibrosis, renal dysfunction, critical illness, transplantation, pregnancy, and/or significant burns. Historically, PK/PD data are underrepresented in these populations, leading to suboptimal dosing recommendations and increased risks of therapeutic failure or toxicity. Herein, we discuss key physiological alterations affecting antimicrobial PK/PD, regulatory challenges, and currently available solutions. To bridge these knowledge gaps, we advocate for broader patient inclusion in clinical trials, improved PK modeling, real-world data collection, and increased investment in precision dosing strategies. Addressing these issues has the potential to enhance patient outcomes, reduce antimicrobial resistance, and improve infectious diseases management. This review serves as a call to action for researchers, clinicians, and policymakers to prioritize PK/PD research in special patient populations.

Background: India has made substantial progress in reducing Plasmodium falciparum malaria cases and has set a target to eliminate malaria by 2030. Although artemisinin-based combination therapy (ACT) treatment remains effective, tracking regional differences in genetic variants associated with antimalarial resistance is required for effective drug policy implementation.

Methods: We analyzed 238 P. falciparum clinical samples from 6 Indian states by sequencing 15 parasite genes associated with reduced drug effectiveness. The method involved nanopore sequencing of target gene amplicons derived from dried blood spots using a highly-sensitive PfMDR15 surveillance panel.

Results: India's historical policy of artesunate-sulfadoxine-pyrimethamine in central India and artemether-lumefantrine in the Northeast has shaped contrasting resistance profiles. In the Northeast, chloroquine resistance persisted at high frequency (Pfcrt K76T and CVIET haplotype; Pfaat1 S258L), alongside quintuple and sextuple Pfdhfr-Pfdhps haplotypes conferring complete sulfadoxine-pyrimethamine resistance. Central India showed variable chloroquine resistance (parasites largely retained wild-type Pfcrt) and emerging lumefantrine tolerance (Pfmdr1 Y184F, Pfaat1 S258L). Interestingly, Delhi (Central India) parasites resembled profiles from the distant Northeast, which borders South East Asia. The detection of Pfaat1 S258L, previously reported only from Africa and associated with reduced lumefantrine susceptibility, suggests convergent evolution under ACT partner-drug pressure. No WHO-validated Pfk13 artemisinin resistance mutations were detected, supporting continued efficacy of ACT.

Conclusions: India's resistance landscape is fragmented, with signals of expanding lumefantrine tolerance and importation or evolution of globally relevant mutations. These findings highlight the importance of integrating molecular genomic surveillance into malaria control policy to monitor and protect ACT effectiveness and advance malaria elimination.

Raoultella species, previously considered an environment bacteria, are emerging as human pathogens. Concerningly, there is a rise in reports of carbapenemase-producing strains. Despite this, specific data on Raoultella planticola and Raoultella ornithinolytica characteristics remain limited. Our study aimed to elucidate the national epidemiology of Raoultella spp. in Israel, characterize their antimicrobial resistance and virulence, and examine the transmission mechanisms of carbapenemases. We conducted a retrospective epidemiological analysis of all Raoultella spp. cases reported to Israel's national surveillance system for carbapenem-producing Enterobacterales between 2011 and 2024. Microbiological characterization and antibiotic susceptibility testing was performed on 32 isolates. Whole-genome sequencing was used to understand the phylogenetic relationships between the isolates, detect antibiotic resistance genes and virulence factors, and identify plasmids. All characterized isolates were found to be multidrug resistant, carried multiple (5-20) antibiotic resistance genes, including at least 1 carbapenemase, and harbored at least 1 plasmid from either Inc or Col incompatibility groups. Two outbreaks were detected among the sequenced isolates. We found increasing incidence of carbapenemase-producing Raoultella cases, and their involvement in healthcare outbreaks.

Our infectious diseases (ID) clinic began a clinic-initiated outpatient parenteral antimicrobial therapy (CI-OPAT) program to avoid unnecessary emergency department visits or inpatient admissions. In this single-center retrospective case series, we describe the treatment of 59 outpatients with CI-OPAT with low rates of complications. These findings suggest that CI-OPAT programs can be safe and effective.