Infectious Diseases and Therapy最新文献

Introduction: This study evaluated the impact of "risk stacking" on COVID-19-related hospitalizations, emergency department/urgent care (ED/UC) visits, and outpatient visits among non-immunocompromised individuals aged 18-49 and 50-64 years compared with immunocompromised individuals and those ≥ 65 years.

Methods: Using Optum Clinformatics^® data, adults were assigned to ≥ 1 category based on underlying CDC-categorized high-risk (HR) conditions: HR-Conclusive (from which immunocompromising conditions were separated), HR-Suggestive, Mixed Evidence, No HR Conditions. The impact of multimorbidity quantities and HR categories on COVID-19 healthcare resource utilization (HCRU) was evaluated.

Results: Overall (n = 10,631,427), the most prevalent conditions were hypertension (HTN; 47.4%), obesity/overweight (31.9%), chronic heart disease (CHD; 28.1%), and diabetes (DBT; 20.3%). COVID-19 HCRU was higher for CHD with DBT, CHD with obesity, and HTN with obesity than for immunocompromised individuals and highest among those aged ≥ 65 years. Multimorbidity across multiple HR categories resulted in greater adjusted risk for COVID-19 HCRU for all ages.

Conclusion: Younger adults with multiple non-immunocompromising comorbidities had greater risk of COVID-19-related HCRU than those with immunocompromising conditions or ≥ 65 years without multimorbidity. Stacking HR comorbidities increased the risk of HCRU. Ensuring broad vaccination and treatment recommendations and access is critical to mitigating severe COVID-19 in HR groups of any age.

Tuberculosis (TB) continues to represent a significant global public health concern, with China being a country that bears the burden of a high incidence of TB cases on a global scale. Although linezolid (LZD) has been recommended for treating drug-resistant tuberculosis (DR-TB), its intolerability and adverse events, such as myelosuppression, neurotoxicity, etc., have limited its long-term usage in anti-TB treatment. Contezolid (CZD), a new generation of oxazolidinone drug, shows comparable or superior antibacterial activity to LZD, with lower risks of myelosuppressive toxicity, neurotoxicity, and lactic acidosis. Its unique metabolic pathway and favorable pharmacokinetic profile render it a promising alternative to LZD for TB treatment. Recent years have seen mounting evidence of the potential of CZD in treating TB. In this paper, the development history, the mode of action, resistance mechanisms, and research progress on CZD for TB treatment are reviewed, aiming to enhance understanding of its role in anti-TB therapy and to provide valuable references for clinical use and future research.

Introduction: Serious bacterial infections among newborns are associated with significant morbidity, mortality, and economic costs. While most newborns fully recover following the acute phase of illness, some develop long-term complications that require medical care. The objective of this real-world study was to estimate acute and long-term healthcare utilization and expenditures among US newborns with bacterial meningitis or sepsis during their birth hospitalization.

Methods: A retrospective matched-cohort design and a US healthcare claims database were employed. Study population comprised newborns who, during their birth hospitalization, had evidence of meningitis or sepsis due to a bacterial pathogen and matched comparison newborns. Study measures included all-cause healthcare utilization and expenditures during the birth hospitalization as well as the 1-year period following discharge.

Results: Among newborns with bacterial meningitis (N = 678), 61% were born prematurely, 27% had low birthweight, and 56% had ≥ 1 high-risk condition; among those with bacterial sepsis (N = 33,478), corresponding values were 48%, 20%, and 33%. During the birth hospitalization, utilization and expenditures were higher (versus comparators) among newborns with meningitis (hospital days, 37 versus 23; intensive care unit [ICU], 97% versus 64%; expenditures, US $423,390 versus $168,861) and sepsis (hospital days, 18 versus 14; ICU, 93% versus 52%; expenditures, $139,973 versus $78,549). Mean levels during the 1-year follow-up period were also markedly higher (versus comparators) among newborns with meningitis (expenditures: by $218,464) or sepsis (expenditures: by $39,259).

Conclusions: Serious bacterial infections among newborns place a substantial burden on the US healthcare system for the treatment of acute illness as well as long-term complications. Interventions targeting the prevention of newborn bacterial infections have the potential to yield significant resource utilization and cost offsets.

Introduction: Adherence to antiretroviral therapy (ART) is crucial for people with HIV (PWH) to maintain health. The Medicare program insures a substantial proportion of PWH in the United States; however, few studies have evaluated ART treatment patterns in this population. This study described treatment persistence and switch patterns among Medicare-insured PWH with low ART adherence or significant treatment gaps prior to re-initiating ART.

Methods: A retrospective cohort study was conducted using data from Medicare Fee-For-Service and Medicare Advantage from January 2017 to December 2022. PWH aged ≥ 18 years with documented treatment experience receiving an index ART regimen of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), dolutegravir/lamivudine (DTG/3TC), dolutegravir/abacavir/lamivudine (DTG/ABC/3TC), or multi-tablet regimens (MTRs; dolutegravir + emtricitabine/tenofovir alafenamide [DTG + F/TAF] or dolutegravir + emtricitabine/tenofovir disoproxil fumarate [DTG + F/TDF]) were included. Study groups of interest included PWH with low adherence (defined as a proportion of days covered [PDC] < 85%) and PWH who had initiated index ART after a ≥ 90-day gap. Treatment nonpersistence (discontinuation or switch) and switch outcomes were evaluated using Kaplan-Meier curves and Cox proportional hazards models.

Results: Of 30,205 treatment-experienced PWH, 6140 had low adherence on the index regimen and 7227 had significant treatment gaps prior to re-initiating ART. In both groups, risk of treatment nonpersistence was significantly lower for PWH indexed on B/F/TAF versus DTG/ABC/3TC and MTRs but similar for DTG/3TC. Risk of treatment switch was lower for those indexed on B/F/TAF versus all other ART regimens evaluated (P < 0.01).

Conclusions: Among Medicare-insured PWH with low adherence or significant gaps in care, those receiving B/F/TAF had a lower risk of switch compared with other ART regimens. Optimizing ART selection to improve persistence and reduce treatment switching remains an important consideration.

Introduction: Pseudomonas aeruginosa is a leading cause of bloodstream infections (BSI) in hospitalized patients. Although it is regarded as an aerobic microorganism, under certain conditions it can switch to anaerobic respiration using other terminal electron acceptors other than oxygen. The study aims to evaluate the clinical and microbiological factors associated with P. aeruginosa isolation in anaerobic blood culture bottles and determine whether anaerobic growth is an independent risk factor for septic shock and 30-day mortality in patients with P. aeruginosa BSI.

Methods: This was a retrospective unicentric study analyzing 734 episodes of P. aeruginosa BSI at a university hospital from 2010 to 2019. Clinical presentation, comorbidities, source of infection, microbiologic data, and outcomes were collected. Anaerobic growth was defined as the isolation of P. aeruginosa in at least one anaerobic blood culture bottle. Multivariate logistic regression models were used to identify factors associated with septic shock and 30-day mortality.

Results: P. aeruginosa was isolated in anaerobic bottles in 19.1% of cases, though it was never exclusively isolated in anaerobic bottles. While median time to positivity (TTP) in anaerobic bottles was significantly longer than in aerobic ones (16.5 h vs. 14.8 h, p < 0.01), TTP in aerobic bottles was shorter when P. aeruginosa was also isolated in anaerobic bottles (12.5 h vs. 15.5 h, p < 0.01). Factors significantly associated with anaerobic growth included chronic kidney disease, longer time of admission, active antibiotic treatment, and several sources of bacteremia (catheter-related, respiratory, and primary bacteremia). Anaerobic growth was independently associated with higher odds of septic shock (OR 2.8, p < 0.01) and increased 30-day mortality (OR 2.3, p < 0.01). Moreover, septic shock and mortality rates were higher when P. aeruginosa grew in both anaerobic bottles.

Conclusions: Anaerobic growth of P. aeruginosa in blood cultures is an independent predictor of septic shock and 30-day mortality in patients with P. aeruginosa BSI. The potential relationship between higher bacterial load and biofilm formation in the source of infection with anaerobic growth of P. aeruginosa may contribute to the observed poorer outcomes.

Introduction: Patient-reported outcomes (PROs) provide important insights into individuals' health and well-being. We report PROs from six observational cohort studies in treatment-experienced people with HIV switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in routine clinical practice.

Methods: Data were pooled from the BICtegravir Single Tablet Regimen (BICSTaR) cohort studies (Asia/Canada/EU/Israel/Japan) and a similarly designed Chinese cohort study (GS-CN-380-5759). Quality of life (QoL; mental/physical health) and HIV treatment satisfaction were self-reported by participants using the generic (non-HIV-specific) 36-item Short Form Health Survey questionnaire and HIV Treatment Satisfaction Questionnaire (HIVTSQ; status [s]/change), respectively. Descriptive statistics and linear mixed models adjusted for potential confounders and interactions, with bootstrapped confidence intervals, were used to analyse PROs through 24 months (12 months for treatment satisfaction).

Results: Of 3724 treatment-experienced participants included, 64.2% were Asian, 89.0% male; median age was 41 years. Baseline Mental Component Summary (MCS) scores were below the population average despite receiving antiretroviral therapy, whereas Physical Component Summary (PCS) scores were above average. At 24 months, observed median MCS score improved from baseline (+ 0.6 [interquartile range [IQR] - 4.3 to + 5.9; p = 0.018]) and median PCS score remained stable (- 0.1 [IQR - 3.3 to + 3.3; p = 0.998]). In all key populations, predicted adjusted MCS/PCS scores showed small improvements or remained stable over time. Treatment satisfaction was high at baseline (median HIVTSQs score 55 [IQR 49-60]), with participants reporting improved treatment satisfaction following the switch to B/F/TAF compared with their previous regimen (+ 27 [19-30] at 12 months). Similar improvements were observed across all key populations.

Conclusion: In this large cohort of people with HIV who switched to B/F/TAF in routine clinical practice, mental and physical health scores improved or remained stable over time and treatment satisfaction improved. Further studies are required to elucidate the clinical relevance of PRO tools and how they relate to QoL in people with HIV. Video abstract available for this article.

Trial registration: ClinicalTrials.gov identifiers NCT03580668 (Canada study) and NCT04009057 (Israel study); EudraCT trial identifier, EUPAS22185 (Europe study). Video abstract available for this article. Quality of life and treatment satisfaction in people with HIV switching to bictegravir/emtricitabine/tenofovir alafenamide: Pooled analysis from observational cohort studies - a video abstract.

Introduction: Aztreonam-avibactam was approved for adults with limited treatment options for multiple infections due to aerobic Gram-negative organisms in the European Union and for complicated intra-abdominal infection in the US, following the phase 3 REVISIT and ASSEMBLE trials. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) assigned minimum inhibitory concentration (MIC) breakpoints for aztreonam-avibactam against Enterobacterales of susceptible ≤ 4 mg/l and resistant > 4 mg/l.

Methods: A comprehensive synthesis of data supporting MIC breakpoint determination is summarized, including: joint probability of pharmacokinetic/pharmacodynamic target attainment (JPTA) analyses (based on population pharmacokinetic modeling) for aztreonam-avibactam dose selection; MIC distributions of target pathogens; clinical and microbiological efficacy outcomes; and exposure-response analyses.

Results: Among 100,228 Enterobacterales isolates, including 2449 metallo-β-lactamase-positive isolates from global surveillance studies (2017-2021), 99% had aztreonam-avibactam MICs of ≤ 8 mg/l. At MIC = 8 mg/l, the predicted JPTA at steady state was 89% to > 99% across subgroups of varying renal function, based on approved doses for aztreonam-avibactam. Clinical trial isolates fell within the same MIC distribution as surveillance studies. There was no evidence of decreased favorable microbiological responses with increasing aztreonam-avibactam MICs in clinical trials; however, in the clinical dataset, there were few Enterobacterales isolates with aztreonam-avibactam MICs of > 4 mg/l.

Conclusions: MIC distributions and JPTA simulations supported a susceptible MIC breakpoint for aztreonam-avibactam against Enterobacterales of ≤ 8 mg/l. However, limited clinical outcomes data for Enterobacterales with aztreonam-avibactam MIC ≥ 4 mg/l justified the more conservative breakpoints established by EUCAST.

Clinical trial registration: ClinicalTrials.gov, NCT03329092 and NCT03580044. Studies/analyses sponsored by Pfizer.

In the phase 3 CONVERT trial, amikacin liposome inhalation suspension (ALIS) plus guideline-based therapy (GBT) achieved greater culture conversion than GBT alone in the treatment of refractory Mycobacterium avium complex pulmonary disease (MAC-PD). In the original analysis of safety data in CONVERT, the rate of hypersensitivity pneumonitis, a prespecified group of adverse events of special interest, was higher in patients receiving ALIS plus GBT (3.1%; n = 7) versus GBT alone (0.9%; n = 1), with half of the cases reported in Japanese patients. We present a summary of serious adverse events of hypersensitivity pneumonitis that investigators deemed related to ALIS treatment in Japanese patients enrolled in CONVERT (n = 3) and its extension study (INS-312; n = 1). Patients were women older than 65 years diagnosed with pneumonitis (n = 3) or interstitial lung disease (n = 1) after initiation of ALIS (range 3-189 days). Following ALIS discontinuation and medical intervention, all four patients recovered from pneumonitis. Additional investigator-collected imaging and serum Krebs von den Lungen 6 (KL-6) data were available for two of these patients, permitting assessment of KL-6 and the potential diagnostic role of radiographic findings. At the time of diagnosis, one patient had ground-glass opacity, and the other patient had consolidation in the right lower lobe of the lung; both patients had serum KL-6 levels > 600 U/mL. Changes in chest radiography and KL-6 levels at the onset of respiratory symptoms during ALIS treatment suggest that these assessments may help guide management strategies for potential hypersensitivity pneumonitis in patients taking ALIS.Clinical Trial Registration: NCT02344004 (CONVERT) and NCT02628600 (INS-312).