Clinical Infectious Diseases最新文献

Doxycycline postexposure prophylaxis (doxy-PEP) is used to prevent chlamydia, syphilis, and gonorrhea infections in sexual and gender minority men and transgender women. We describe a systematic process for developing algorithms that allow for the identification of doxy-PEP prescriptions. Using an identified algorithm will allow improved monitoring of implementation and effectiveness.

Background: Before the advent of effective antiretroviral therapy, intensive care unit (ICU) admission rates for people with advanced human immunodeficiency virus HIV disease (AHD) were low, reflecting high mortality and limited treatment options. Despite improvements in ICU and HIV care, longitudinal outcome data in critically ill people with AHD are limited.

Methods: We performed a retrospective cohort study of ICU admissions in Australia and New Zealand between January 1993 and December 2022 in patients with a comorbid diagnosis of AHD. AHD was defined according to Acute Physiology and Chronic Health Assessment-IIIj (APACHE-IIIj), requiring an HIV diagnosis plus AHD-defining complication. Descriptive analysis was performed. Longitudinal changes in mortality were reported. Admissions were stratified by decade.

Results: There were 1505 ICU admissions with comorbid AHD over the study period. Between the first and third decades, the Sequential Organ Failure Score increased (median 3, interquartile range [IQR] 2-5 vs median 4, IQR 2-6, P < .001), as did patient age (median 41 years, IQR 34-52 vs median 53 years, IQR 44-63, P < .001). The proportion of patients with 1 or more chronic comorbidities using APACHE-IIIj scoring increased over time (18% vs 26%; P = .009). Crude hospital mortality reduced significantly from 36% in 1993-2002 to 14% in 2013-2022 (P < .001). Mortality improvements remained significant after adjustment for acute and chronic illness severity (using APACHE-IIIj risk of death) and hospital type (adjusted odds ratio of death by decade 0.43; 95% confidence interval, .35-.53).

Conclusions: Despite advances in HIV care, a subset of people with AHD require ICU admission. Mortality in this group has improved by more than 50%.

Background: Stagnating decreases in Kaposi sarcoma (KS) among men with HIV (MWH) following Treat-All policies necessitate evaluating changes in clinical drivers of KS. We examined clinical factors and their associations with KS rates among MWH in North America.

Methods: Among MWH in the North American AIDS Cohort Collaboration on Research and Design, we estimated annual KS rates (per 100 000 person-years [PY]) by viral suppression (<200 copies/mL), CD4 count (<500 vs ≥500 cells/mm3), and time since ART initiation (<1 year/naive vs ≥1 year) from 2009-2019. We quantified associations between clinical factors and KS rates using negative binomial regression, estimating incidence rate ratios (IRRs) with 95% CIs. Among MWH with KS, we estimated average annual percentage changes (AAPCs) in clinical factor distribution using joinpoint regression.

Results: There were 61 155 MWH (370 624 PY) contributing 262 KS diagnoses. KS decreased from 132 to 43 cases per 100 000 PY between 2009 and 2019. Viral suppression (IRR2009: .09 [95% CI: .04-.20]; IRR2019: .69 [.31-1.54]), recent/no ART initiation (IRR2009: .14 [.07-.30]; IRR2019: 1.16 [.53, 2.56]), and CD4 count ≥500 cells/mm3 (IRR2009: .13 [.05-.31]; IRR2019: .44 [.18-1.10]) were associated with reduced KS rates, attenuating over time. Unsuppressed viral load at KS diagnosis decreased by 10.6% (-15.8%, -4.8%) as did those on ART ≤1 year/naive (70%-40%; AAPC: -6.3% [-13.8%, 2.1%]).

Conclusions: Our findings underscore the importance of early HIV diagnosis/treatment in reducing KS burden. Attenuating associations with HIV factors indicate that those successfully managing HIV increasingly represent KS patients. KS drivers are evolving, requiring patient/population-level monitoring.

Doxycycline postexposure prophylaxis (doxy-PEP) reduces the risk of bacterial sexually transmitted infections among men who have sex with men and transgender women. In the United States, doxy-PEP is in an early stage of integration into clinical practice, and national guidelines for its use were recently released. The goal of this manuscript is to provide practical guidance for clinicians who are considering or currently prescribing doxy-PEP. We address 5 clinical questions using post hoc analyses of data from the DoxyPEP randomized controlled trial and discuss the potential implications and limitations of each question with the goal of informing clinical practice and implementation of doxy-PEP programs. The questions address patient eligibility criteria for doxy-PEP, the expected benefit and associated doxy-PEP doses for the average patient, the initial number of doses prescribed, and laboratory monitoring of persons taking doxy-PEP.

Bacterial sexually transmitted infections (STIs) including syphilis, chlamydia, and gonorrhea continue to rise in key populations despite prevention efforts. Doxycycline post-exposure prophylaxis (doxy-PEP) has demonstrated efficacy in reducing syphilis and chlamydia in men who have sex with men (MSM) and transgender women (TGW), with variable effects on gonorrhea depending on background levels of tetracycline resistance. However, some sexual health organizations recommend limiting widespread implementation due to antimicrobial resistance concerns. Given the demonstrated efficacy of Doxy-PEP among MSM/TGW, implementation efforts should not be hindered by concerns related to antimicrobial resistance. Instead, efforts to reduce tetracycline use in animal feed are warranted, as well as efforts to reduce overuse in other medical conditions. Doxy-PEP implementation should include efforts related to evaluation and monitoring of local antimicrobial resistance including N. gonorrhoeae. This approach upholds the ethical principle of beneficence (providing efficacious care to patients) while addressing public health concerns related to antimicrobial resistance.

Background: The diagnosis of pulmonary tuberculosis (TB) remains challenging in sputum-scarce and sputum-negative patients. Tongue swabs represent a promising non-invasive alternative specimen type that could overcome this diagnostic limitation. This study aimed to evaluate the performance of molecular detection of Mycobacterium tuberculosis (Mtb) from tongue swabs in this clinically challenging population.

Methods: In this study, We enrolled 625 sputum scarce individuals with presumptive TB from four Chinese TB hospitals. For each participant, paired tongue swab and bronchoalveolar lavage fluid (BALF) specimens were collected. Tongue swab specimens were analyzed using MTB-specific PCR assay, while BALF specimens underwent comprehensive evaluation using both microbiological reference standard (MRS) and Xpert MTB/RIF assay.

Results: Tongue swab testing demonstrated high diagnostic accuracy with 79.9% sensitivity (95% CI: 73.9-84.8) and 99.5% specificity (95% CI: 98.0-99.9) against the MRS, and 81.7% sensitivity (95% CI: 75.7-86.6) with 97.6% specificity (95% CI: 95.5-98.8) against Xpert MTB/RIF. Notably, simulation modeling revealed that when the proportion of sputum-scarce patients exceeded 10%, the tongue swab PCR strategy outperformed conventional sputum-only Xpert MTB/RIF testing in overall case detection rates.

Conclusions: Tongue swab-based PCR represents a non-invasive, accurate, and highly specific diagnostic approach for tuberculosis, particularly in sputum-scarce or sputum-negative individuals. While this study demonstrates its superior performance in such populations, further optimization of sampling protocols and molecular assays is needed to improve detection sensitivity in cases with low bacillary loads. Integrating tongue swab testing into routine TB diagnostic algorithms could enhance case detection, strengthen drug resistance surveillance, and contribute to reducing transmission.

Background: In this phase 3 trial of an investigational maternal respiratory syncytial virus prefusion F protein-based vaccine (RSVPreF3-Mat), a higher rate of preterm birth was observed in the vaccine (6.8%) versus the placebo group (4.9%). Trial enrollment and vaccination were stopped. Results of investigations into this safety signal were reported previously. Here, we describe end-of-trial efficacy, immunogenicity, and safety results.

Methods: Women 18-49 years old were randomized 2:1 to receive 1 dose of RSVPreF3-Mat (n = 3557) or placebo (n = 1771) at 240/7-340/7 weeks' gestation. Primary outcomes were any and severe medically assessed RSV-associated lower respiratory tract disease (MA-RSV-LRTD) in infants until 6 months postbirth and safety until 12 months postbirth. Other efficacy outcomes were evaluated, along with immunogenicity (until 6 months postpartum/birth) and safety in mothers and infants.

Results: Efficacy (with 95% credible interval) in infants until 6 months postbirth was 65.5% (37.5%-82.0%) against any MA-RSV-LRTD, 69.0% (33.0%-87.6%) against severe MA-RSV-LRTD, and 50.1% (-3.6% to 75.8%) against RSV hospitalization; it waned over time thereafter. Efficacy against MA-RSV-LRTD was 47.8% (-25.8% to 77.3%) in low- and middle-income and 75.9% (46.1%-91.5%) in high-income countries. RSVPreF3-Mat induced a substantial increase in RSV-A neutralization titers in mothers, with efficient transplacental transfer of antibodies that persisted in infants until at least 6 months postbirth.

Conclusions: Consistent with the high titers of transplacentally transferred antibodies, this trial suggests a reduced risk of any/severe MA-RSV-LRTD and RSV hospitalization until 6 months postbirth in infants born to mothers immunized with RSVPreF3-Mat during pregnancy. However, vaccine development was terminated due to an identified preterm birth risk. Clinical Trials Registration. NCT04605159.