Open Forum Infectious Diseases最新文献

Background: Antimicrobial resistance is rampant in low- and middle-income countries. Recent data from Princess Marina Hospital (PMH), Botswana, revealed that 100% of pediatric surgical unit patients received antimicrobials inappropriately.

Methods: We implemented a quality improvement initiative to improve antimicrobial use in children admitted to PMH's pediatric surgical ward. With key stakeholders, we developed clinical pathways (CPs) to standardize antimicrobial use across common surgical diagnoses. A CP booklet, informed by the World Health Organization (WHO) Access, Watch, and Reserve (AWaRe) guideline, was distributed to prescribers. We conducted weekly prospective antimicrobial use audits over 1 year, from 3 months pre-CP implementation to 9 months post-CP implementation.

Results: A total of 1099 pediatric surgical patients were admitted and 374 (34.0%) required antimicrobials. The WHO Access group accounted for 360 antibiotic courses (72.4%) and the Watch group for 137 (27.6%), a total of 497. Overall, appropriate antimicrobial use improved significantly (pediatric surgery, 33 [50.8%] vs 99 [93.4%]; orthopedics, 3 [10.3%] vs 26 [89.7%]; neurosurgery, 5 [27.8%] vs 13 [72.2%]; and ear, nose, and throat, 4 [33.3%] vs 19 [95.0%]; each P < .001) in the postimplementation period except for maxillofacial-dental patients (1 [25.0%] vs 3 [75.0%]; P = .264). Improvements were observed across provider categories and years of experience: medical officers (28 [42.4%] vs 38 [91.0%]), interns (7 [33.3%] vs 20 [87.0%]), and specialists (11 [26.2%] vs 64 [97.0%]); years of experience: <2 years (9 [32.1%] vs 22 [91.7%]), 2-5 years (3 [25.0%] vs 50 [92.6%]), and >5 years (34 [38.2%] vs 154 [92.2%]) (P < .001 for each).

Conclusions: Appropriate antimicrobial use improved post-CP implementation. Expanding CPs with ongoing antimicrobial stewardship education will ensure sustained improvement.

Background: Typhoid fever remains a public health concern in Harare City, Zimbabwe. Recurrent outbreaks are driven by inadequate water, sanitation, and hygiene infrastructure. In 2019, the typhoid conjugate vaccine (TCV) was introduced. The TCV impact on typhoid epidemiology, antimicrobial resistance (AMR), Salmonella Typhi population, and effectiveness across districts and age groups remains understudied.

Methods: Data from 3401 typhoid cases during 2017-2024 were analyzed. Attack rates, risk ratios, AMR, and vaccine effectiveness across prevaccine (2017-2019) and postvaccine (2020-2024) periods were compared. Analysis was stratified by district, vaccination coverage, and age groups. Genomic characteristics of Salmonella Typhi strains isolated postvaccination were investigated and compared to prevaccine populations.

Results: Attack rates for the Western district, which reported 70.8% of cases, decreased from 1373/100 000 before TCV to 341/100 000 after (risk ratio: 0.40, P ≤ .0001). Subdistricts had attack rates of 1783 (Glen View), 1687 (Mufakose), and 1145 (Budiriro) per 100 000 before vaccination and 223, 33, and 364/100 000, respectively, after (risk ratio: 0.22, 0.03, 0.48, respectively, P < .0001). The 0-15 age group showed vaccine effectiveness of 81.2% (95% confidence interval, 71.2-88.8), compared to 61.4% (95% confidence interval, 54.3-68.1) across all ages. Genomic comparison of Salmonella Typhi isolates pre- and postvaccination did not indicate changes in bacterial population. AMR phenotypic data and genomic prediction indicated lower resistance to antibiotics postvaccination.

Conclusions: TCV reduced typhoid incidence, particularly in high-burden areas and children. No shift in the Salmonella Typhi population was observed. Ongoing transmission underscores need for integrated measures, including human-resource capacity, improved water, sanitation, and hygiene infrastructure, research on vaccine performance variability, and refined multisectoral interventions.

Background: HIV reservoirs, dysregulated cytokine profile, and gut barrier damage persist despite suppressive combination antiretroviral therapy (cART). Whether initiating cART during primary HIV infection (PHI) mitigates these pathological processes remains unclear.

Methods: We studied 55 individuals with PHI at baseline (T0), after 12 (T12), and 48 weeks (T48) of cART, 18 individuals with chronic HIV infection (CHI) and 10 sex-matched people without HIV (PWOH). Total HIV DNA was measured in peripheral blood mononuclear cells (PBMCs) using ddPCR, while cytokines profiles (IL-2, IL-4, TNF-α, IFN-γ) were measured in plasma by Luminex and antigen-specific T-cell responses were assessed in PBMCs of a subset of participants by intracellular cytokine staining. Microbial translocation markers (EndoCab, 1,3-β-D-glucan, lipopolysaccharide-binding protein [LBP], soluble CD14 [sCD14]) and gut barrier integrity markers (E-cadherin, I-FABP) were measured in plasma by ELISA, at each corresponding time point. Statistical analyses included Friedman tests with Dunn's multiple comparisons, Wilcoxon paired tests, and Mann-Whitney tests, as appropriate.

Results: At baseline, both groups displayed a cytokine profile characterized by elevated IL-4 levels compared with PWOH, with individuals with PHI showing significantly higher IL-2 levels and comparable IFN-γ and TNF-α levels to individuals with CHI. Over 48 weeks of cART, IL-4 and IL-2 declined only in individuals with PHI, yet, remained elevated compared with PWOH, whereas cytokine levels remained largely stable in individuals with CHI. Conversely, antigen-specific CD4⁺ T-cell responses remained mainly Th1-skewed, with minimal IL-4 production. Individuals with PHI showed lower baseline sCD14, comparable to PWOH, which further declined during cART, whereas sCD14 remained elevated in individuals with CHI compared with PWOH. Markers of microbial translocation (LBP, 1,3-β-D-glucan) remained stable in individuals treated in PHI and comparable to PWOH but increased in individuals treated in CHI over time. E-cadherin levels were consistently lower in individuals with PHI, similar to PWOH. In contrast, I-FABP showed a non-significant decline over time only in individuals with PHI, while remaining higher in both individuals with PHI and CHI compared with PWOH.

Conclusions: Early cART initiation in individuals with PHI reduces viral reservoirs and limits gut barrier disruption and microbial translocation but fails to restore the systemic cytokine landscape compared with PWOH. These findings support the benefits of prompt treatment initiation during acute infection to limit HIV reservoir size and preserve mucosal integrity.

[This corrects the article DOI: 10.1093/ofid/ofaf620.].

Background: More than 1 million Americans reside in skilled nursing facilities (SNFs). Antimicrobial transition errors among patients transferred from hospital to SNFs pose safety risks and may lead to poor outcomes, but data on such errors are limited.

Methods: We conducted a retrospective cohort study of infectious diseases clinics from 1 June 2020 through 30 November 2023 at the Los Angeles County Department of Health Services, a large safety-net health system. We performed logistic regression analyses to identify factors associated with antimicrobial transition errors and poor infection outcomes.

Results: We screened records of 6865 clinic patients, among whom 112 were SNF residents who were receiving post-hospital discharge antimicrobials. Mean age was 62 years, 37% were female, and 57% were Hispanic/Latino. Transition errors occurred in 32 (29%) patients. Common medications associated with errors were penicillin class (39%), tetracycline class (38%), and daptomycin (36%). In our multivariable model, age, Charlson Comorbidity Index score, number of medications, Centers for Medicare & Medicaid Services SNF rating, and therapy duration were not significantly associated with transition errors. Older age was the only independent predictor of poor infection outcome (P & .02). There was a nonsignificant trend between antimicrobial transition errors and poor infection outcome (odds ratio, 1.63 [95% confidence interval, .58-4.81]).

Conclusions: Nearly one-third of patients transitioning from hospitals to SNFs on antimicrobials experienced ≥1 antimicrobial transition error. We did not identify risk factors for antimicrobial transition errors. The trend toward an association between antibiotic transition errors and poor infection outcomes warrants further investigation in more robust data sets.

Background: Transfeminine persons in the United States face a high burden of human immunodeficiency virus (HIV), yet national data on preexposure prophylaxis (PrEP) use remain limited. We examined PrEP utilization, adherence, and persistence and reasons for never using PrEP among a national sample of transfeminine persons.

Methods: Sexually active transfeminine persons aged ≥15 years without HIV were recruited online through the Transgender Women's Internet Survey and Testing (TWIST) Study, a national cross-sectional survey conducted between June 2023 and October 2024. Multivariable Poisson regression was used to estimate adjusted prevalence ratios for characteristics associated with current PrEP use. Reasons for never using PrEP were examined descriptively by age group.

Results: Among 1656 participants, 6% were currently using PrEP and 86% had never used PrEP. Among current users (n = 96), 94% used oral PrEP and 6% used long-acting injectable (LA) PrEP. Among the 32 participants who reported using <30 daily PrEP doses in the past 30 days, 25% indicated that they were using event-driven (on-demand) PrEP, taking it only when they anticipated having sex. In multivariable models, current PrEP use was higher among participants aged ≥40 years, Black participants, and participants reporting a sexually transmitted infection diagnosis, multiple sexual partners, illicit drug use, or prescribed medication use. Common reasons for never using PrEP among participants aged 15-24 years included insurance-related privacy and disclosure concerns and transportation barriers, while among participants aged ≥25 years, reasons included loss of insurance, side-effect concerns, and monogamous partnerships.

Conclusions: PrEP uptake among transfeminine persons remains low, with distinct age-specific barriers. Tailored interventions are needed. LA PrEP may help address challenges related to adherence and disclosure, particularly among younger individuals.

Background: People living with HIV-1 (PLWH) have an increased risk of cardiovascular disease (CVD), influenced by chronic inflammation, immune dysregulation, and antiretroviral therapy (ART). B cells regulate immune responses, but their contribution to HIV-associated atherosclerosis remains poorly defined.

Methods: In a cross-sectional study, we enrolled 40 PLWH and 60 people without HIV (PWoH) in Uganda, matched 1:1.5 for age and CVD risk. Peripheral blood mononuclear cells were profiled by mass cytometry to define immune cell subsets. Coronary computed tomography angiography quantified coronary artery disease using the segment stenosis score (SSS). We used multivariable hurdle regression to estimate the effect sizes of immune clusters, atherosclerotic cardiovascular disease (ASCVD) risk score, HIV status, and gender.

Results: Median age was 60 years, with no difference by HIV status. People living with HIV had a lower proportion of CCR7^- naïve B cells than PWoH (median 1.5% vs 1.8%; P-value adjusted [padj] = .03). Across all participants, higher CCR7^- naïve B cells (ratio = 0.55, P = .02), CXCR3⁺CX3CR1⁺ B cells (ratio = 0.54, P = .03), and plasmablasts (ratio = 0.57, P = .003) were associated with lower SSS. HIV-positive status was linked to nearly 3-fold higher SSS (P < .01). In stratified analyses, classical monocytes (CD14⁺CD16^-) correlated with higher SSS among PLWH. When classical monocytes were held at the median, higher CCR7^- naïve B cells were protective in PLWH (ratio = 0.55, P = .02).

Conclusions: This exploratory study suggests that lower frequencies of naïve B cells in PLWH are associated with differences in subclinical atherosclerosis. However, the mechanisms cannot be inferred from this study.

Background: There are few leptospirosis incidence studies despite such estimates being central to accurate burden of disease estimation. We used data from the multicenter Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE) study to make leptospirosis incidence estimates from new sites.

Methods: Febrile patients aged ≥2 months in Laos, Malawi, Mozambique, and Zimbabwe were enrolled and underwent standardized clinical and exposure assessment. Acute and convalescent sera were tested by Leptospira microscopic agglutination test and acute plasma by lfb1 polymerase chain reaction (PCR). Participants with ≥4-fold rise in antibody titer between acute and convalescent sample, or Leptospira PCR positive for the lfb1, had confirmed leptospirosis. Leptospirosis incidence was estimated after adjusting for incomplete enrollment of febrile patients, availability of paired sera, and use of study healthcare facilities by febrile patients based on healthcare utilization data from community controls.

Results: Leptospirosis incidence (95% CI) per 100 000 population per year was 1302 (1011, 1677) in Laos, 1337 (874, 2044) in Malawi, 187 (85, 409) in Mozambique, and could not be calculated for Zimbabwe. Sensitivity analysis restricted to pre-COVID years of 2018 and 2019 produced similar estimates of incidence to that of the whole study period.

Conclusions: Leptospirosis incidence was high at the Laos, Malawi, and Mozambique sites and at the upper end of published incidence estimates from the Asia and Africa regions. We recommend more leptospirosis incidence studies be done in areas lacking data to strengthen leptospirosis global burden of disease estimates and to stimulate progress on diagnosis, management, and control.

Nonpolio enteroviruses are the most common cause of meningitis in children. We conducted a retrospective case series of long-term outcomes in 243 children between 1 January 2013 and 31 December 2023 across 4 tertiary centers in London. Adverse outcomes were associated with the absence of fever at presentation (odds ratio [OR], 4.65; 95% CI, 1.03-20.83), the presence of seizures (OR, 7.40; 95% CI, 1.05-51.96), and the presence of comorbidities at baseline (OR, 5.27; 95% CI, 1.18-23.47). Full recovery was seen in 153 of 160 (95.6%) children who were <3 months of age. These data may help clinicians to counsel parents and policy makers on streamlining care pathways following hospital discharge.

Pathogen load is considered fundamental to infection pathobiology but is unobserved or inadequately measured. We used latent variable modeling to characterize HIV-associated tuberculosis mycobacterial load in 519 inpatients. Tests on urine and blood, not sputum, showed substantial covariance. Summarizing covariance via measurement models estimated pathogen loads with stronger correlation with host inflammation and mortality than traditional measures such as blood culture time to positivity.