Clinical Infectious Diseases最新文献

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.

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.

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: 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.

Acute bacterial prostatitis (ABP) and chronic bacterial prostatitis (CBP) are poorly defined clinical entities, and diagnosis can be challenging. A clinical diagnosis of ABP can be made in the setting of an acute urinary tract infection (UTI) with systemic illness and evidence of prostatic involvement as defined by prostatic tenderness or fluctuance on digital rectal examination or prostatic abscess identified on imaging. Management includes a minimum of 2 weeks of antibiotics with surgical intervention reserved for refractory cases or prostatic abscess (depending on size). Chronic bacterial prostatitis should be suspected in a male patient with chronic urinary symptoms or recurrent UTIs. Diagnostic evaluation should include a 4- or 2-glass Meares-Stamey test, with a positive test confirming the diagnosis. Management includes 6 weeks of antibiotics. Surgery can be considered for particularly refractory cases. Future research into ABP and CBP can address questions about epidemiology, role of radiographic imaging, and duration of antimicrobial therapy.

Background: The impact of pharmacokinetic variability of cabotegravir (CAB) and rilpivirine (RPV) long-acting (LA) injectable therapy on virological outcomes remains controversial. This study aimed to characterize the variability of CAB and RPV trough concentrations (Ctrough) and to identify the predictors of suboptimal exposure and virologic failure (VF) in a large real-world cohort.

Methods: We conducted a multicenter observational study including people with human immunodeficiency virus type 1 (HIV-1) initiating LA-CAB/RPV as maintenance therapy from January to December 2022, in whom CAB and RPV plasma Ctrough were determined as part of therapeutic drug monitoring (TDM).

Results: A total of 1674 CAB and 1687 RPV Ctrough measurements were collected from 736 people with HIV-1 (PWH). Significant interindividual variability in concentrations was observed. At month 1/month 3, 20%-30% of PWH had Ctrough <1120 ng/mL for CAB and 32 ng/mL for RPV. Predictors of lower Ctrough were body mass index (BMI) ≥30 kg/m2 and female sex at month 1, and only male sex at steady state. After a median follow-up of 12 (interquartile range, 9-16) months, VF occurred in 2.5% of PWH. At month 6 and month 12, VF was significantly associated with the presence of at least 2 risk factors (obesity, suboptimal Ctrough) (odds ratio [OR], 4.6, P = .047; OR, 5.15, P = .014), and CD4 nadir (OR, 0.56, P = .008; OR, 0.5, P = .001).

Conclusions: Our large real-world study confirms significant variability in CAB and RPV exposure, with BMI and sex as key predictors of lower Ctrough. Suboptimal CAB and RPV Ctrough, particularly in people with obesity, increases the risk of VF during the first year of treatment, highlighting the usefulness of TDM in clinical practice.

Background: Recent trials have demonstrated that shortened 4-month treatment durations are effective for the majority of people with tuberculosis (TB). However, there is a population of patients with TB who require longer treatment durations. Prospectively identifying those who require shorter versus longer treatment durations would support evaluation and implementation of optimized regimens.

Methods: We analyzed data from the RIFASHORT TB treatment-shortening noninferiority trial to define a TB phenotype classification. The RIFASHORT trial primary outcome was reanalyzed using the protocol-defined noninferiority criterion of 8 percentage points, stratifying by those classified as having limited or extensive disease.

Results: Xpert MTB/RIF semiquantitative bacterial burden in combination with TB disease involvement grading on chest X-ray achieved the strongest differentiation between relapse and nonrelapse. The extensive disease TB phenotype (high semiquantitative bacterial burden and extensive TB disease on X-ray) accounted for one-quarter of the RIFASHORT trial population and more than half of all posttreatment TB relapses (13/23). For the limited TB disease phenotype (a semiquantitative bacterial burden other than high or no extensive TB disease on X-ray), the experimental 4-month 1200-mg rifampicin-containing regimen met the protocol-defined noninferiority criterion in both modified intention-to-treat (adjusted risk difference: -1.3%; 95% CI, -6.7% to 4.0%) and per protocol analyses (1.7%; 95% CI, -3.8% to 7.1%).

Conclusions: The TB phenotype classification derived here successfully identified three-quarters of RIFASHORT trial participants for whom a 4-month 1200-mg rifampicin regimen was noninferior to the 6-month standard of care. A definitive phase III randomized trial of disease-stratified rifampicin-based TB treatment is justified.