Background Quantification of recurrence risk following successful treatment is crucial to evaluating regimens for multidrug- or rifampicin-resistant (MDR/RR) tuberculosis (TB). However, such analyses are complicated when some patients die or become lost during post-treatment-follow-up. Methods We analyzed data on 1,991 patients who successfully completed a longer MDR/RR-TB regimen containing bedaquiline

Introduction During the 2022 mpox outbreak, the province of Quebec, Canada prioritized first doses for pre-exposure vaccination of people at high mpox risk, delaying second doses due to limited supply. We estimated single-dose mpox vaccine effectiveness (VE) adjusting for virus exposure risk based only on surrogate indicators available within administrative databases (e.g. clinical record of sexually

We estimated the risk of death from coronavirus disease 2019 in vaccinated compared with unvaccinated patients. The risk of death was reduced 44% after 1 dose of the Pfizer-BioNTech BNT162b2 vaccine, 55% after 1 dose of the Oxford-Astrazeneca ChAdOx1 vaccine, and 69% after 2 doses of the BNT162b2 vaccine. This is above the protection provided against infection.

Background Tuberculosis prevention using isoniazid (IPT) is recommended for people with HIV, yet data on the safety of first-trimester pregnancy exposure are limited. Methods Planned secondary analysis in a TB prevention trial of adverse pregnancy outcomes among participants assigned to 9-month IPT who became pregnant during (IPT-exposed) or after (unexposed) IPT. Regression models compared binary

Background Early in the COVID-19 pandemic, peak viral loads coincided with symptom onset. We hypothesized that in a highly immune population, symptom onset might occur earlier in infection, coinciding with lower viral loads. Methods We assessed SARS-CoV-2 and influenza A viral loads relative to symptom duration in symptomatic adults (>16y) presenting for testing in Georgia (4/2022-4/2023; Omicron variant

Background Hematogenous vertebral osteomyelitis (HVOM) is an incompletely understood complication of Staphylococcus aureus bacteremia (SAB). Methods Eligible SAB patients with and without HVOM were prospectively enrolled from 1995 through 2019 at Duke University Health System. HVOM was diagnosed either radiographically or microbiologically. Multivariable logistic regression analysis was performed to

Background Growing evidence suggests that some coronavirus disease 2019 (COVID-19) survivors experience a wide range of long-term postacute sequelae. We examined the postacute risk and burden of new-incident cardiovascular, cerebrovascular, and other thrombotic complications after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a highly vaccinated multiethnic Southeast Asian

We report 12 patients with persistent viremia on oral antiretroviral therapy who were initiated on injectable cabotegravir/rilpivirine (iCAB/RPV) without oral lead-in. All patients achieved viral suppression without any virologic rebound. iCAB/RPV may be considered as an option for patients unable to maintain suppression on oral antiretroviral therapy.

More than a decade after the Consolidated Standards of Reporting Trials group released a reporting items checklist for non-inferiority randomized controlled trials, the infectious diseases literature continues to underreport these items. Trialists, journals, and peer reviewers should redouble their efforts to ensure infectious diseases studies meet these minimum reporting standards.

Background Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) are frequently caused by multidrug-resistant organisms. Patient-centered endpoints in clinical trials are needed to develop new antibiotics for HABP/VABP. Desirability of outcome ranking (DOOR) is a paradigm for the design, analysis, and interpretation of clinical trials based on a patient-centered, benefit-risk

Background Widespread outbreaks of person-to-person transmission of hepatitis A virus (HAV), particularly among people who inject drugs (PWID), continue across the United States and globally. However, the herd immunity threshold and vaccination coverage required to prevent outbreaks is unknown. We aimed to use surveillance data and dynamic modeling to estimate herd immunity thresholds among PWID in

The recently updated SHEA/IDSA/APIC practice recommendations for MRSA prevention in acute care facilities list contact precautions (CP) for patients known to be infected or colonized with MRSA as an “essential practice”, meaning that it should be adopted in all acute care facilities. We argue that existing evidence on benefits and harms associated with CP do not justify this recommendation. There are

Background Several clinical trials of tuberculosis preventive treatment (TPT) for household contacts of patients with multidrug- or rifampin-resistant tuberculosis (MDR/RR-TB) are nearing completion. The potential benefits of delivering TPT to MDR/RR-TB contacts extend beyond the outcomes that clinical trials can measure. Methods We developed an agent-based, household-structured TB and MDR/RR-TB transmission

Background Native vertebral osteomyelitis (NVO) caused by Staphylococcus aureus is associated with high risk of treatment failure and increased morbidity. The role of rifampin-based therapy for the treatment of this condition is controversial. The goal of this systematic review and meta-analysis is to explore the efficacy and safety of rifampin-based therapy for the treatment of S. aureus NVO. Methods

Background Allogeneic hematopoietic cell transplant recipients (allo-HCTR) with positive CMV serology may have false positive results due to blood product transfusions associated passive immunity. Methods This is a single-center cohort study including consecutive adult allo-HCTR (01.01.2018-31.12.2022) with negative baseline (at hematologic malignancy diagnosis) and indeterminate or low-positive (CMV-IgG-titer:

We describe a case of congenital tuberculosis in an extremely premature baby, with rapid molecular detection of a pre-XDR pattern of drug resistance. The baby was treated successfully with a regimen including bedaquline and delamanid, drugs not previously described in the treatment of congenital TB.

Glucocorticoids are widespread anti-inflammatory medications used in medical practice. The immunosuppressive effects of systemic glucocorticoids and increased susceptibility to infections are widely appreciated. However, the dose-dependent model frequently used may not accurately predict the risk of infection in all patients treated with long-term glucocorticoids. In this review, we examine the risks

Background HPTN 083/084 trials showed up to 88% increased efficacy of long-acting cabotegravir (CAB-LA) versus continuous oral tenofovir/emtricitabine (TDF/FTC). However, CAB-LA’s high price limits the number who can be treated within fixed prevention budgets. Global HIV prevention budgets are highly limited, with TDF/FTC widely available as a low-cost generic. In randomised clinical trials, event-driven

Background Standalone nucleic acid amplification tests (NAATs) are frequently used to diagnose Clostridioides difficile infections (CDI), although they may be unable to distinguish colonization from disease. A two-stage algorithm pairing NAATs with toxin immunoassays (Toxin) may improve specificity. We evaluated clinical outcomes of patients who were NAAT+/Toxin + versus NAAT+/Toxin- and treated versus

We describe bedside-to-bench immunological and genetic elucidation of defective pyroptosis attributable to novel Caspase 4 defect mediating pathogen-triggered inflammatory programmed cell death, in setting of severe pneumonia and abscess-forming melioidosis in an overtly healthy host failing to clear Burkholderia pseudomallei, and how targeted adjunctive biological therapy led to successful outcome

Background Providers must balance effective empiric therapy against toxicity risks and collateral damage when selecting antibiotic therapy for patients receiving hematopoietic cell transplant (HCT). Antimicrobial stewardship (AMS) interventions during HCT are often challenging due to concern for undertreating potential infections. Methods In an effort to decrease unnecessary carbapenem exposure for

In this cohort study conducted in Hong Kong where both bivalent and monovalent formulations of BNT162b2 were available, there was no significant differences in the mortality or hospitalization between those who received bivalent and monovalent mRNA as second boosters. Bivalent and monovalent mRNA boosters appear equally protective against clinical outcomes.

The rapid growth of telehealth services has brought about direct-to-consumer telemedicine platforms, enabling patients to request antibiotics online without a virtual or face-to-face consultation. While telemedicine aims to enhance accessibility, this trend raises significant concerns regarding appropriate antimicrobial use and patient safety. In this viewpoint, we share our first-hand experience with

Background The clinical and microbial factors associated with K. pneumoniae bloodstream infections (BSI) are not well characterized. Prior studies have focused on highly resistant or hypervirulent isolates, limiting our understanding of K. pneumoniae strains that commonly cause BSI. We performed a chart review and whole genome sequencing (WGS) to investigate the clinical characteristics, bacterial

Background Single-dose benzathine penicillin G (BPG) is the preferred therapy for early syphilis, but poorer serologic responses have been observed among people with HIV (PWH). No enhanced regimen has previously been shown to improve serologic outcomes of early syphilis. Methods We conducted a retrospective study to compare the treatment responses to single-dose BPG combined with 7-day doxycycline

Chronic hepatitis B, a major cause of liver disease and cancer, affects over 250 million people worldwide. Currently there is no cure, only suppressive therapies. Efforts to develop finite curative HBV therapies are underway, consisting of combinations of multiple novel agents +/- nucleos(t)ide reverse transcriptase inhibitors. The HBV Forum convened a webinar in July 2021, and subsequent working group

Background The epidemiology of COVID-19 continues to develop with emerging variants, expanding population-level immunity, and advances in clinical care. We describe changes in the clinical epidemiology of hospitalized COVID-19 and risk factors for critical outcomes over time. Methods We included adults aged ≥18 years from 10 states hospitalized with COVID-19 June 2021-March 2023 when multiple SARS-CoV-2

Hepatitis C virus (HCV) elimination is an important global public health goal. However, the United States (US) is not on track to meet the World Health Organization’s 2030 targets for HCV elimination. Recently, the White House proposed an HCV elimination plan that includes point-of-care (POC) HCV RNA testing, which is currently in use in many countries, but is not approved in the US. POC HCV RNA testing

Introduction In high-burden settings, low-complexity screening tests for tuberculosis (TB) could expand the reach of community-based case-finding efforts. The potential costs and cost-effectiveness of approaches incorporating these tests are poorly understood. Methods We developed a microsimulation model assessing three approaches to community-based case-finding in hypothetical populations (India-

Background Seroprevalence and risk factors for Human Herpesvirus-8 (HHV-8) infection among HIV-negative men who have sex with men (MSM) on pre-exposure prophylaxis (PrEP) have not been well characterized. Our objectives were to assess the prevalence and incidence of HHV-8 infection in MSM enrolled on PrEP and assess viral shedding in seropositive participants. Methods The ANRS IPERGAY study enrolled

Objectives Molnupiravir and nirmatrelvir-ritonavir were the first oral antiviral agents to demonstrate reduced hospitalization or death in patients with SARS-CoV-2, but patients with immunocompromised conditions were not well-represented. The objective of this study was to characterize and compare the clinical outcomes of US Veterans with immunocompromised conditions prescribed oral antivirals to those

Background Amphotericin B is the gold standard treatment for severe mycoses. A new orally delivered, less-toxic formulation of amphotericin has been developed. Methods In our randomized clinical trial, we tested oral lipid nanocrystal (LNC) amphotericin B (MAT2203, Matinas Biopharma) vs intravenous (IV) amphotericin for human immunodeficiency virus–associated cryptococcal meningitis in 4 sequential

Among 43 pregnant women receiving multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment with bedaquiline and/or delamanid, 98% had favorable treatment outcomes. Of 31 continued pregnancies, 81% had live births with no reported malformations, and 68% of neonates had normal birth weights. Effective MDR/RR-TB treatment during pregnancy can improve maternal outcomes without harming

Background Obesity is increasingly prevalent among people with HIV (PWH) and can possibly result in suboptimal antiretroviral drug (ARV) exposure and response. However, this has not been thoroughly evaluated given that obese PWH are underrepresented in clinical trials. We performed virtual trials using physiologically based pharmacokinetic (PBPK) modelling combined with observed clinical data to provide

Background Doxycycline post-exposure prophylaxis (doxyPEP) reduces bacterial sexually transmitted infection (STI) incidence in people with HIV (PWH) or using HIV preexposure prophylaxis (PrEP). Given concerns about widespread antibiotic use, we identified doxyPEP prescribing strategies to minimize use while maximizing impact on STIs. Methods We used electronic health records of gay and bisexual men

We review key concepts in the diagnosis, treatment, and follow-up of individuals with neurosyphilis. We describe the epidemiology of syphilis in the United States, highlight populations that are markedly affected by this infection, and attempt to estimate the burden of neurosyphilis. We describe the cardinal clinical features of early and late (tertiary) neurosyphilis and characterize the clinical

Background Sepsis surveillance using electronic health record (EHR)-based data may provide more accurate epidemiologic estimates than administrative data, but experience with this approach to estimate population-level sepsis burden is lacking. Methods This was a retrospective cohort study including all adults admitted to publicly-funded hospitals in Hong Kong between 2009-2018. Sepsis was defined as

Background A low-level risk of intussusception following rotavirus vaccination has been observed in some settings and may vary by vaccine type. We examined the association between RotaTeq vaccination and intussusception in low-income settings in a pooled analysis from five African countries that introduced RotaTeq into their national immunization program. Methods Active surveillance was conducted in

Resistance of SARS-CoV-2 to antivirals was shown to develop in immunocompromised individuals receiving remdesivir. We describe an immunocompromised patient who was treated with repeated and prolonged courses of nirmatrelvir and developed de-novo E166V/L50F mutations in the Mpro region. These mutations were associates with clinical and virological treatment failure.

HIV-associated immunosuppression may increase risk of hospitalization with mpox. Among persons diagnosed with mpox in the state of Georgia, we characterized the association between hospitalization with mpox and HIV status. People with HIV and CD4 < 350 cells/mm3 or who were not engaged in HIV care had increased risk of hospitalization.

The HIV workforce continues to face a crisis, particularly in the southern United States. Adding to known issues of administrative burden and less competitive compensation, recent anti-LGBTQ+ legislation threatens the already strained HIV workforce. HIV care providers advocate for all aspects of their patient’s lives, including those needing gender-affirming care. The recent legislative targets against

In a cross-sectional analysis of 354 Ugandan children (age 12-48 months) infected with Schistosoma mansoni, we assessed relationships between infection intensity and nutritional morbidities. Higher intensity was associated with an increased risk for anemia (RR = 1.05, CI 1.01-1.10) yet not associated with risk for underweight, stunting, or wasting.

In a propensity-score-weighted cohort of 183 adults with carbapenem-resistant Enterobacterales bacteremia at 24 United States hospitals, patients receiving short-courses of active therapy (7-10 days, median 9 days) experienced similar odds of recurrent bacteremia or death within 30 days as those receiving prolonged courses of active therapy (14-21 days, median 14 days).

The optimal treatment of prosthetic joint infection (PJI) remains uncertain. Patients undergoing debridement and implant retention (DAIR) receive extended antimicrobial treatment, and some experts leave patients at perceived highest risk of relapse on suppressive antibiotic therapy (SAT). In this narrative review, we synthesize the literature concerning the role of SAT to prevent treatment failure

Global elimination of hepatitis C virus (HCV) will be difficult to attain without an effective HCV vaccine. Controlled human infection (CHI) studies with HCV were not considered until recently, when highly effective treatment became available. However, now that successful treatment of a deliberate HCV infection is feasible, it is imperative to evaluate the ethics of establishing a program of HCV CHI

Following the discovery of hepatitis C virus (HCV) in 1989, 3 decades of basic, translational, and clinical research culminated in the development of direct-acting antiviral (DAA) therapy—curative oral treatment for HCV infection. The availability of DAA therapy revolutionized HCV clinical management, including acute (duration of infection <6 mo) and recent (duration of infection <12 mo) infection

Background In 2019, about 58 million individuals were chronically infected with hepatitis C virus. Some experts have proposed challenge trials for hepatitis C virus vaccine development. Methods We modeled incremental infections averted through a challenge approach, under varying assumptions regarding trial duration, number of candidates, and vaccine uptake. We computed the benefit-risk ratio of incremental

The design of a clinical trial for a controlled human infection model (CHIM) to accelerate hepatitis C virus (HCV) vaccine development requires careful consideration. The design of a potential approach to HCV CHIM is outlined, involving initial sentinel cohorts to establish the safety and curability of the viral inoculum followed by larger cohorts to establish the spontaneous clearance rate for each

In a hepatitis C virus (HCV)–controlled human infection model (CHIM), healthy volunteers are inoculated with HCV and then treated. Residual hepatocellular carcinoma (HCC) risk after viral clearance is an important consideration when evaluating the CHIM. We estimate HCC risk in spontaneously cleared HCV and in noncirrhosis after sustained virological response (SVR) to HCV treatment in a systematic review

Ethical human subjects research requires participants to be treated safely and respectfully, yet much bioethical debate takes place without participants. We aim to address this gap in the context of controlled human infection model (CHIM) research. Based upon our own experience as study participants, and bolstered by a survey of 117 potential hepatitis C virus CHIM participants, we present ideas to

For any controlled human infection model (CHIM), a safe, standardized, and biologically relevant challenge inoculum is necessary. For hepatitis C virus (HCV) CHIM, we propose that human-derived high-titer inocula of several viral genotypes with extensive virologic, serologic, and molecular characterizations should be the most appropriate approach. These inocula should first be tested in human volunteers

Controlled human infection model trials for hepatitis C virus represent an important opportunity to identify correlates of protective immunity against a well-characterized inoculum of hepatitis C virus and how such responses are modified by vaccination. In this article, we discuss the approach to immunological monitoring during such trials, including a set of recommendations for optimal sampling schedule

Background Tuberculosis (TB) disease has been associated with pregnancy complications. However, the potential impact of TB infection (TBI) on pregnancy outcome is unknown. To investigate this, we conducted a register-based study in immigrant women screened with QuantiFERON assays for TBI in antenatal care in Sweden. Methods Women with history of immigration from TB-endemic countries were eligible for

Background For persons entering congregate settings optimal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) arrival surveillance screening method, nucleic acid amplification (NAAT) versus rapid antigen detection test (RADT), is debated. To aid this, we sought to determine the risk of secondary symptomatic coronavirus disease 19 (COVID-19) among military trainees with negative arrival NAAT

Background Many clinical guidelines recommend that clinicians use antibiograms to inform empiric antimicrobial therapy. However, hospital antibiograms are typically generated by crude aggregation of microbiologic data, and little is known about an antibiogram’s reliability in predicting antimicrobial resistance (AMR) risk at the patient-level. We aimed to assess the diagnostic accuracy of antibiograms

HIV-positive individuals lost to follow-up from particular clinics may not be lost to care (LTC). After linking Vanderbilt’s Comprehensive Care Clinic cohort to Tennessee’s statewide HIV surveillance database, LTC decreased from 48.4% to 35.0% at 10 years. Routine surveillance-linkage by domestic HIV clinics would improve LTC and retention measure accuracy.

We reported a case of human infection with the H3N8 avian influenza virus, who had multiple myeloma and died of severe infection. Genome analysis showed multiple gene mutations and reassortments without mammalian-adaptive mutations. This report suggested that avian influenza (A/H3N8) virus infection could be lethal for person who were immunocompromised.

Background An early report has shown the clinical benefit of the asymptomatic preoperative SARS-CoV-2 screening test and some clinical guidelines recommended it; however, the cost-effectiveness of asymptomatic screening was not evaluated. We aimed to investigate the cost-effectiveness of universal preoperative screening of asymptomatic patients for SARS-CoV-2 using polymerase chain reaction (PCR) testing

Background Immunocompromised patients are at high risk of severe COVID-19 and death, yet treatment strategies for immunocompromised patients hospitalized for COVID-19 reflect variations in clinical practice. This comparative effectiveness study investigated the effect of remdesivir treatment on inpatient mortality among immunocompromised patients hospitalized for COVID-19 across all variants of concern

Background Scarce data are available comparing infective endocarditis (IE) following surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). This study aimed to compare the clinical presentation, microbiological profile, management, and outcomes of IE after SAVR vs. TAVR. Methods Data were collected from the “Infectious Endocarditis after TAVR International” (enrollment