Infectious Diseases and Therapy最新文献

Introduction: The treatment of Stenotrophomonas maltophilia bloodstream infections (BSI) remains challenging due to the organism's intrinsic multidrug resistance and the potential side effects of commonly used first-line antibiotics.

Methods: Here, we describe four cases of S. maltophilia BSI treated with cefiderocol (≥ 72 h) in different Italian hospitals. Additionally, we conducted a PubMed search to identify other studies reporting cases of S. maltophilia BSI managed with cefiderocol.

Results: We reviewed a total of 8 cases of S. maltophilia BSI [median age 52.5 years (Q1-Q3 27.5-61.0), 50% males] treated with cefiderocol, including ours. BSI sources were mainly central venous catheters (62.5%) and the lower respiratory tract (25.0%). Cefiderocol was used as first-line therapy in 87.5% of patients (7/8), with a median treatment duration of 14 days (IQR 6.2-16.0). Combination therapy was administered in 62.5% of cases. Infection source control was required in 75.0% and achieved in 40.0%. Clinical success was observed in 62.5% of patients, with microbiological eradication in 87.5%. In-hospital mortality occurred in 37.5% of cases, with one death directly attributable to S. maltophilia. No significant differences were observed in terms of outcomes between cefiderocol monotherapy and combination therapy.

Conclusions: Based on our findings and a review of the literature, cefiderocol-based regimens show promise as an effective treatment option for S. maltophilia BSI, warranting further investigation in larger studies.

Introduction: The POET trial demonstrated that moving from intravenous to oral antibiotics in stable patients with left-sided infective endocarditis (IE) was noninferior to fully parenteral treatment. However, it did not compare outpatient strategies.

Methods: The OraPAT-IE GAMES trial is a noninferiority, multicenter, randomized, open-label study aimed to compare partial oral versus outpatient parenteral antibiotic therapy (OPAT) for consolidation of antibiotic treatment in left-sided IE. A total of 342 stable patients with IE caused by selected micro-organisms will eventually be included. After a minimum of 10 days of parenteral treatment, stable patients are randomized to oral therapy or OPAT. The primary end-point is a composite of all-cause mortality, unplanned cardiac surgery, relapse of positive blood cultures and/or unplanned hospital admission. Patients are followed-up for 6 months after completing antibiotic therapy.

Planned outcome: This trial seeks to demonstrate the equivalent efficacy of the two outpatient strategies currently available for stable patients with IE in the consolidation phase of antibiotic treatment.

Conclusion: In a global context of limited healthcare resources and a sustained increase in elderly and frail patients, it is of great importance to demonstrate the effectiveness and safety of outpatient management strategies that could reduce the duration of conventional hospitalizations with their potential complications and inherent costs.

Trial registration: EudraCT: 2020-001024-34.

Clinicaltrials: gov identifier: NCT05398679.

Introduction: Patients with depression were shown to be at increased risk of herpes zoster (HZ). However, an in-depth description of depression as a risk factor for HZ, postherpetic neuralgia (PHN), and HZ recurrence is lacking. The goal of this study was to quantify the risk of HZ, PHN, and HZ recurrence in people with depression and among depression-related subgroups in Germany.

Methods: Using health insurance claims data from 2012 to 2021 from a large German claims database, people ≥ 18 years old diagnosed with depression were identified and matched to control persons without depression using a rolling cohort design. Incidence rates (cases per 1000 person-years [PYs]) and incidence rate ratios (IRRs) were calculated using Poisson models.

Results: Overall, 1,768,701 people with depression were matched to controls without depression. HZ incidence rates were higher in people with depression (10.51 cases/1000 PYs) than in people without depression (9.04 cases/1000 PYs). Overall, people with depression had a significantly increased risk of HZ (IRR = 1.16; p < 0.0001), PHN (IRR = 1.16; p < 0.0001), and HZ recurrence (IRR = 1.22; p < 0.0001). IRRs were highest in the 18 to 49 years age group (IRR HZ = 1.24; p < 0.0001; IRR PHN = 1.35; p < 0.0001). IRRs for HZ were highest in people with mental disorder comorbidities (IRR = 1.23; p < 0.0001).

Conclusions: A diagnosis of depression is associated with an increased risk of HZ, PHN, and HZ recurrence. People with depression should be considered when developing HZ vaccination recommendations.

Introduction: This study compared the calculated vancomycin area under the curve (AUC_0-24) using trapezoidal and non-trapezoidal first-order pharmacokinetic equations.

Methods: This retrospective observational study included adult patients with documented MRSA bacteremia who received ≥ 48 h of intravenous vancomycin and had two consecutive serum levels after the first dose. AUC_0-24 was calculated using trapezoidal and non-trapezoidal equations. Correlation and agreement between methods were assessed using Pearson's correlation coefficient (r) and Bland-Altman plots. Significant predictors (p < 0.05) from simple linear regression were included in a multiple linear regression model to evaluate their impact on AUC_0-24 for both methods.

Results: Fifty-two patients were included. The median age was 63 years (interquartile range [IQR]: 50-73), and the median vancomycin clearance was 4 l/h (IQR: 2-6). Median vancomycin AUC_0-24 was 399 mg∙h/l (IQR: 257-674) for the trapezoidal method and 572 mg∙h/l (IQR: 466-807) for the non-trapezoidal method. There was a strong correlation between the methods (r = 0.87 [95% CI, 0.79-1]; P < 0.01), but Bland-Altman analysis showed poor agreement, with a bias of - 198 mg∙h/l and 95% limits of agreement from - 482 to 86 mg∙h/l. In multiple linear regression, total daily dose and vancomycin clearance were independent predictors of AUC_0-24 for both methods, with a stronger impact on non-trapezoidal AUC_0-24 (adjusted R² = 0.70) than trapezoidal AUC_0-24 (adjusted R² = 0.59).

Conclusions: Trapezoidal and non-trapezoidal equations are not interchangeable for estimating vancomycin AUC_0-24. The trapezoidal method consistently results in lower AUC_0-24 estimates than the non-trapezoidal method.

The growing interest in leveraging artificial intelligence (AI) tools for healthcare decision-making extends to improving antibiotic prescribing. Large language models (LLMs), a type of AI trained on extensive datasets from diverse sources, can process and generate contextually relevant text. While their potential to enhance patient outcomes is significant, implementing LLM-based support for antibiotic prescribing is complex. Here, we specifically expand the discussion on this crucial topic by introducing three interconnected perspectives: (1) the distinctive commonalities, but also the crucial conceptual differences, between the use of LLMs as assistants in scientific writing and in supporting antibiotic prescribing in real-world practice; (2) the possibility and nuances of the expertise paradox; and (3) the peculiarities of the risk of error when considering LLMs to support complex tasks such as antibiotic prescribing.

Introduction: Among people with HIV (PWH), real-world data on the long-term renal function evolution while receiving tenofovir alafenamide (TAF)-containing antiretroviral therapy (ART) remain scarce.

Methods: PWH who initiated or were switched to TAF-containing ART and controls who received non-tenofovir-containing ART were included for follow-up. We retrospectively collected demographic, clinical, and laboratory data, including estimated glomerular filtration rate (eGFR), urine β-2 microglobulin, and urine protein-to-creatinine ratio (UPCR). The association between the duration of ART exposure and change of eGFR was compared in locally estimated scatterplot smoothing (LOESS) regression. Factors associated with an excess decline of eGFR (defined as a decline > 2.5 ml/min/1.73 m² per year; or > 25% throughout the observation) among TAF-receiving PWH were also evaluated.

Results: Overall, 2422 PWH receiving TAF-containing regimens and 252 controls were included, with the median follow-up duration being 4.8 and 5.4 years, respectively. In the LOESS regression, the predicted change of eGFR at weeks 240 was - 8.0 (95% CI, - 9.1 to - 6.8) ml/min/1.73 m² for TAF group, compared to - 11.1 ml/min/1.73 m² (95% CI, - 15.4 to - 6.7) for non-TAF group. In the TAF group, 183 (7.6%) experienced an excessive renal function decline. Furthermore, the levels of urine β-2 microglobulin and UPCR remained stable throughout the observation. A higher plasma HIV RNA level, old age, presence of clinically significant proteinuria throughout observation, and having a higher eGFR at baseline were associated with an excessive decline of eGFR among TAF-receiving PWH.

Conclusions: Our study suggests that long-term exposure to TAF-containing ART was not associated with augmented eGFR declines among PWH.

Introduction: Pneumococcal conjugate vaccines (PCVs) were first introduced in the paediatric United Kingdom (UK) immunisation programme in 2006 which led to significant declines in invasive pneumococcal disease (IPD) caused by targeted serotypes. Although paediatric PCVs provide some indirect protection to adults, a significant IPD burden remains in older adults. Here, we compared three adult (65+ years-old) and risk group (2-64-year-old) vaccination scenarios, namely a continuation of the status quo with PPSV23 vaccination, using the recently licensed-in-adults PCV20, or using the new adult-focused 21-valent PCV, V116.

Methods: A population-level compartmental dynamic transmission model (DTM) was adapted to the UK setting. The model described Streptococcus pneumoniae carriage transmission dynamics and disease progression in the presence of age- and serotype-specific pneumococcal vaccines. We calibrated the DTM to age- and serotype-specific IPD data in the UK and used the model to make projections under the different adult vaccination scenarios while keeping PCV13 immunisation in children.

Results: The calibrated model yielded reasonable parameter values and model fits that closely matched observed IPD dynamics. Among 65+ year-olds, 10-year model projections predicted that the routine use of V116 would reduce IPD incidence by 15.5%, while PCV20 would reduce IPD incidence by 8.9% and the continued use of PPSV23 would increase incidence by 3.83%. There was a notable decrease in IPD incidence in the serotypes unique to V116. In the serotypes included in PCV20 but not V116, the model did not predict a resurgence of IPD.

Conclusions: Projections revealed that in adults, V116 led to significantly greater reductions in IPD in the 65+ year-old population compared with PCV20 or PPSV23.

Introduction: Invasive Escherichia coli disease (IED) incidence has increased over recent years among aging populations and has rising antimicrobial resistance. Here, we report on a comparative, cross-sectional, retrospective analysis of US patients with IED to quantify IED-related healthcare resource utilization (HCRU), costs, and impact on health-related quality of life (HRQoL).

Methods: This study included Kaiser Permanente Northwest (KPNW) members aged ≥ 60 years enrolled between July 2019 and January 2020. Patients were divided into three groups: Group 1 had experienced a recent IED episode (≤ 3 weeks before enrollment); Group 2 had experienced a former IED episode (13-18 months before enrollment); Group 3 was at risk with no prior history of IED. Data were collected from electronic hospital records, a patient survey, and the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire. Mean costs were adjusted according to individual follow-up.

Results: Patient characteristics were generally consistent across Groups 1 (n = 289), 2 (n = 319), and 3 (n = 340). Inpatient hospitalization was observed in 84%, 44%, and 15% of patients in Groups 1, 2 and 3, respectively. Mean direct costs per patient (per 30-day follow-up) were $17,168, $2530, and $1094 in Groups 1, 2, and 3, respectively. Mean total costs per patient in the year following an IED episode (Group 2) were $35,034 vs. $16,163 in the at-risk Group 3. HRQoL was poor for patients with recent IED, with a mean EQ-5D-5L utility index value of 0.25 on the worst day of illness. During a 12-month follow-up period, rehospitalization rates and mean number of antibiotic prescriptions were ~ threefold higher for patients who recovered from IED vs. those at risk.

Conclusions: These data demonstrate substantial short- and long-term impacts of IED on HCRU, IED-related costs, and HRQoL. Additional research is needed to further value the impact of novel IED prevention strategies.

Introduction: In 2024, the vaccination strategy against pneumococcal disease in the Dutch paediatric population was changed from the 10-valent pneumococcal conjugate vaccine (PCV) (PCV10) to a 15-valent PCV (PCV15) under a 2 + 1 schedule. We aimed to assess whether switching from PCV15 under a 2 + 1 schedule to 20-valent PCV (PCV20) under a 3 + 1 schedule in the Dutch paediatric national immunisation programme (NIP) would yield economic savings and health benefits.

Methods: A multiple-cohort population model with an annual cycle and 10-year time horizon was adapted for the Dutch population from a societal perspective. Discounting was set at 3.0% and 1.5% for costs and benefits, respectively. Medical and societal costs were calculated, along with cases of invasive and non-invasive pneumococcal disease, and quality-adjusted life years (QALY) for PCV15 and PCV20, from which, the incremental cost-effectiveness ratio (ICER) per QALY was calculated for PCV20 versus PCV15 to determine the economic benefits of PCV20. The model assumptions were tested in probabilistic and deterministic sensitivity analyses, as well as a series of scenario analyses.

Results: Both medical and societal cost of disease were substantially lower with PCV20 versus PCV15 (incremental cost-savings of €130,113,010 and €61,593,168, respectively), with total incremental cost-savings of €29,365,696 when considering the cost of the vaccination programme. With an overall QALY gain of 33,232, the ICER per QALY placed PCV20 as the dominant strategy, as it was both more effective and less costly than PCV15. PCV20 was estimated to result in 57,657 fewer pneumococcal disease cases across invasive and non-invasive disease and 1561 fewer disease-related deaths. The sensitivity and scenario analyses demonstrated the robustness of the model results.

Conclusion: This cost-effectiveness analysis demonstrated that switching from PCV15 2 + 1 to PCV20 3 + 1 in the Dutch paediatric NIP would reduce both the clinical burden and projected costs of pneumococcal disease over 10 years.

Introduction: Little is known about the risk of invasive E. coli disease (IED) after elective urologic procedures. We estimated the risk of IED after selected urologic procedures in patients with or without antibiotic prophylaxis, and in controls with no urologic or other surgical procedures.

Methods: The Komodo Research Database (01/01/2021-06/30/2023) was used to identify patients ≥ 60 years old with selected urological procedures (index: first urologic procedure date) and randomly selected controls without surgical procedures (index: random date). Patients with urologic procedures were classified into two cohorts based on whether or not they received antibiotic prophylaxis within 14 days prior to and on index date. Entropy balancing adjusted for differences between groups in selected patient characteristics over 6 months pre-index (baseline). IED rates within 30 days post-index were assessed based on recorded diagnosis of E. coli sepsis (ICD-10-CM: A41.51); odds ratios (OR) were estimated using weighted logistic regression. Sensitivity analyses within 90 days and using broader claims-based algorithm for IED were performed.

Results: Overall, 141,418 patients had urologic procedures with antibiotic prophylaxis, 200,062 had them without antibiotic prophylaxis, and 424,254 had no procedures. Within 30 days post-index, IED rates were 0.48% and 0.72% among patients with or without antibiotic prophylaxis, respectively, vs. 0.02% among those without any procedures. Among patients with urologic procedures,  > 70% of IED events occurred within 30 days. Patients who had urologic procedures without prophylaxis had a higher risk of developing IED than those with prophylaxis (OR = 1.50, 95% confidence interval [CI: 1.37-1.65]), while patients without any procedures had a lower risk than those with urologic procedures and prophylaxis (OR = 0.04, 95% CI [0.03-0.05]). Similar results were obtained in sensitivity analyses.

Conclusions: Urologic procedures were associated with an increased IED risk even with antibiotic prophylaxis. Results suggest an unmet need for additional preventative measures to reduce the burden of IED after urologic procedures.