Clinical Infectious Diseases最新文献

Uncomplicated urinary tract infections can cause significant physical and emotional burden for patients, with high rates of recurrence. The challenges of treating uncomplicated urinary tract infections are exacerbated by rising antimicrobial resistance in key uropathogens, primarily Escherichia coli, on a global scale. Clinicians should consider drug, pathogen, and host-related factors when selecting the most appropriate therapy.

Background: Coadministering vaccines can effectively enhance vaccination uptake in adults. Despite the potential benefits, there is limited data supporting this practice. We investigated the immunogenicity and safety of coadministering coronavirus disease 2019 (COVID-19) messenger RNA, influenza, and pneumococcal (PPSV23) vaccines in adults.

Methods: As part of the national vaccination program, 3104 adults received a fourth dose (second booster) of an messenger RNA COVID-19 vaccine alone or coadministered with an influenza vaccine, with or without PPSV23 from January to December 2022. We measured severe acute respiratory syndrome coronavirus 2 anti-spike and anti-receptor binding domain (RBD) immunoglobulin G (IgG) concentrations and neutralization activity before and 1 month after vaccination. We estimated the odds of a ≥2-fold geometric mean fold rise (GMFR) and adverse events (AEs) using logistic regression models.

Results: The median age of the 3104 participants was 70 years (interquartile range: 60-77); 1670 (54%) were female. Anti-spike IgG GMFRs were 1.95, 1.56, and 1.42, whereas for neutralization activity, values were 8.99, 12.42, and 8.23, in the COVID-19, COVID-19 + influenza, and COVID-19 + influenza + PPSV23 groups, respectively. The adjusted odds of a ≥2-fold anti-spike IgG GMFR were 0.64 (P < .001) and 0.43 (P < .001), and for neutralization activity, 0.96 (P = .833) and 0.97 (P = .954), for COVID-19 + influenza and COVID-19 + influenza + PPSV23, respectively. The odds for anti-RBD GMFRs followed similar patterns. Systemic AEs were more common in the COVID-19 + influenza + PPSV23 group (adjusted odds ratio: 2.04, P < .001), though no serious AEs were reported.

Conclusions: Coadministering COVID-19, influenza, and PPSV23 vaccines seems feasible, without significantly impairing neutralizing antibody responses. These findings support the recommendation for vaccine coadministration in adults.

Background: Sexually transmitted infections (STIs) have been shown to facilitate human immunodeficiency virus (HIV) transmission and acquisition. HPTN 083, a global clinical trial, demonstrated superiority of long-acting cabotegravir (CAB-LA) versus daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV prevention among transgender women and cisgender men who have sex with men. This analysis assessed whether CAB-LA maintained protective efficacy when bacterial STIs (syphilis, rectal/urethral gonorrhea, and chlamydia) were present.

Methods: STI events per 100 person-years were calculated, including by subgroups (age, race/ethnicity, gender, education, treatment arm, drug use, alcohol use, region/country, condom usage, partner number, marital status, baseline STI). Association between baseline factors and STI incidence was modeled using Poisson regression. Cox proportional hazards modeling with STI status as a time-varying covariate was used to evaluate potential interactions between STI status and the relative efficacy of CAB-LA versus TDF/FTC.

Findings: Among 3859 participants, overall STI incidence rate was 50.7 infections/100 person-years. STIs were diagnosed in 1562 (40.5%) participants; 79% of STIs occurred in 25% of the participants. STI incidence was not different by preexposure prophylaxis arm. In the final multivariable model, age, region, race, education level, marital status, and baseline STI were associated with incident STI (P < .05). HIV incidence was lower with CAB-LA versus TDF/FTC with or without STIs (hazard ratios 0.37 and 0.31, respectively), with no significant interaction between STIs and the HR for HIV incidence (P = .75).

Conclusions: In a large preexposure prophylaxis trial with high STI incidence, CAB-LA maintained robust protective efficacy relative to TDF/FTC in the setting of bacterial STIs.

Background: Approximately 1.5 billion doses of novel oral polio vaccine type 2 (nOPV2) have been administered in response to circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks since 2021. Although infants are eligible to receive the vaccine from birth, the induction of intestinal mucosal immunity by nOPV2 in newborns has not been directly evaluated.

Methods: In a randomized, placebo-controlled, phase 2 clinical trial in Bangladesh (2020-2021), 215 healthy newborns received 2 doses of either nOPV2 (n = 110) or placebo (sucrose; n = 105), at birth (0-3 days) and 4 weeks later. Intestinal mucosal antibody responses were assessed by measuring poliovirus type 2 (PV2)-specific neutralizing activity and immunoglobulin (Ig)A levels in stool collected biweekly from birth to 8-weeks.

Results: Newborns vaccinated with 2 doses of nOPV2 had strong intestinal mucosal antibody responses that differed significantly from the placebo group (P < .0001 for PV2-specific neutralization from 2 weeks onward and P ≤ .007 for PV2-specific IgA from 4 weeks onward). Positive PV2-specific neutralization in stool (titers ≥16) was detected in 51.8% (57/110) of nOPV2-vaccinated newborns at 4 weeks and 90.0% (99/110) at 8 weeks (4 weeks after the second dose). Notably, PV2-specific antibody titers following the second dose were very similar for newborns who did and did not have first dose responses (P = .67 for neutralization and P = .38 for IgA at 8 weeks).

Conclusions: Vaccination with 2 doses of nOPV2 in neonates induced strong intestinal mucosal antibody responses. In cVDPV2 outbreak settings, neonatal administration of nOPV2 may be a strategy to enhance population-level intestinal mucosal immunity.

Background: While neutropenic enterocolitis (NEC) is a well-known life-threatening complication during intensive chemotherapy, its incidence, impact, and outcome on specific at-risk populations remain ill defined.

Methods: We report 178 NEC episodes during 1963 myeloablative chemotherapy courses among 1259 adult patients with acute myeloid (AML) or lymphoblastic (ALL) leukemia or receiving autologous hematopoietic stem cell transplantation (auto-HCT) for lymphoma or multiple myeloma. Risk factors were assessed by multivariate logistic regression models.

Results: Most NEC cases (93.3%) occurred during AML induction (n = 92; 13.8% of chemotherapy course) and auto-HCT (n = 74; 9.5%). Independent risk factors for NEC during AML induction included high-dose corticosteroids (OR = 2.07; 95% CI: 1.29-3.30; P = .002), elevated circulating blasts at the time of diagnosis (>50 Giga/L; OR = 2.02; 95% CI: 1.15-3.56; P = .02), and use of azacitidine (OR = 2.45; 95% CI: 1.01-5.90; P = .05); purine-based regimens (eg, FLAG-Ida) were an independent protective factor (OR = .27; 95% CI: .15-.47; P < .001). Independent risk factors after auto-HCT included BEAM (carmustine, etoposide, cytarabine, and melphalan) versus another conditioning protocol (OR = 3.28; 95% CI: 1.98-5.43; P < .001) and age (OR = 1.03/year; 95% CI: 1.01-1.06; P = .007). For both AML induction and auto-HCT, NEC was associated with longer hospitalization (P = .03 and <.001), sepsis (quick SOFA ≥2; P = .03 and <.001), fungemia (P < .001 and P = .01), and intensive care admission (P = .03 and <.001, respectively). NEC was associated with increased in-hospital mortality during AML induction (6.5% vs 2.4%; P = .04) but not during auto-HCT (P = .3).

Conclusions: The incidence of NEC depended on chemotherapeutic regimens, with higher occurrence during standard "7 + 3" AML induction and BEAM conditioning for auto-HCT. NEC was associated with longer hospitalization and increased morbidity, but 30-day mortality was lower than previously reported.

Long-acting injectables (LAIs) for HIV prevention and treatment could dramatically improve health outcomes and health equity for people with HIV and those who could benefit from pre-exposure prophylaxis. Despite widespread acceptability and demand by providers and potential users of LAIs, implementation has been extremely limited since the introduction of cabotegravir/rilpivirine, the first LAI for HIV treatment, in January 2021, and long-acting cabotegravir, the first LAI for HIV prevention, in December 2021. We report results of a provider survey, conducted by the HIV Medicine Association, which identified LAI implementation barriers related to health insurance processes, staffing and administrative support, drug costs and acquisition, and access for individuals who are uninsured. We provide policy recommendations to address those barriers and facilitate broad and equitable access to LAIs for HIV prevention and treatment, which will be necessary to achieve the goals of the US Ending the HIV Epidemic initiative.

Background: There is paucity of information on the role of cytomegalovirus (CMV) infection as a cause of stillbirths or childhood deaths in low- and middle-income countries (LMICs). We investigated attribution of CMV disease in the causal pathway to stillbirths and deaths in children <5 years of age in 7 LMICs participating in the Child Health and Mortality Prevention Surveillance (CHAMPS) network.

Methods: We analyzed stillbirths and decedents enrolled between December 2016 and July 2023. Deaths were investigated using postmortem minimally invasive tissue sampling with histopathology and molecular diagnostic investigations of tissues and body fluids, along with review of clinical records. Multidisciplinary expert panels reviewed findings and reported on the causal pathway to death.

Results: CMV was detected in 19.5% (1140/5841) of all evaluated deaths, including 5.0% (111/2204), 6.2% (139/2229), 41.2% (107/260), 68.1% (323/474), and 68.2% (460/674) of stillbirths, neonates (deaths <28 days postnatal), early infants (28 to <90 days), late infants (90 to <365 days), and children (12 to <60 months), respectively. CMV disease was attributed in the causal pathway to death in 0.9% (20/2204) of stillbirths, 0.8% (17/2229) of neonates, 13.1% (34/260) of early infants, 9.7% (46/474) of late infants, and 3.3% (22/674) of children. Decedents with CMV disease, compared with those without CMV disease in the causal pathway, were more likely to have severe microcephaly (38.2% vs 21.1%; adjusted odds ratio [aOR], 2.2 [95% confidence interval {CI}, 1.3-3.6]) and to have human immunodeficiency virus (HIV) (36.9% vs 6.2%; aOR, 10.9 [95% CI, 6.5-18.5]).

Conclusions: CMV disease is an important contributor to deaths during infancy and childhood and is often associated with severe microcephaly and HIV infection. Improving management of CMV in children with HIV and a vaccine to prevent CMV are needed interventions.