Clinical Microbiology and Infection最新文献

Background: Infections are a major cause of morbidity in children with primary or secondary immunodeficiency, and have a negative impact on overall outcome.

Objectives: This narrative review presents select paediatric-specific aspects regarding the clinical impact, diagnosis, management, and follow-up of infectious complications in patients with primary and secondary immunodeficiencies.

Sources: PubMed until January 2024 and searched references in identified articles including the search terms: infection, immunodeficiency or cancer, diagnostics, antimicrobial agents, bacteria or fungus or virus, and follow-up.

Content: Major advances have been made in the early detection and management of patients with primary immunodeficiency, and multiple analyses report in children with cancer on risk groups and periods of risk for infectious complications. Although many diagnostic tools are comparable between children and adults, specific considerations have to be applied, such as minimizing the use of radiation. Antimicrobial drug development remains a major challenge in the paediatric setting, which includes the establishment of appropriate dosing and paediatric approval. Last, long-term follow-up and the impact of late effects are extremely important to be considered in the management of immunocompromised paediatric patients.

Implications: Although infectious disease supportive care of immunocompromised children and adolescents has considerably improved over the last three decades, close international collaboration is needed to target the specific challenges in this special population.

Objectives: To investigate whether there is a dose-dependent association between empiric dexamethasone and outcome in viral meningitis.

Methods: Observational cohort study of adults hospitalized for viral meningitis, both with and without a microbiologically confirmed diagnosis, in Denmark between 2015 and 2020. Dose-dependent associations between dexamethasone (one dose = 10 mg) and an unfavourable outcome (Glasgow Outcome Scale score 1-4) at 30 days after discharge were assessed using weighted logistic regression. Entropy balancing was used to compute weights.

Results: Of 1025 included patients, 658 (64%) did not receive dexamethasone, 115 (11%) received 1-2 doses, 131 (13%) received 3-4 doses, and 121 (12%) received ≥5 doses. Among patients treated with dexamethasone, the median number of doses was higher for those without an identified pathogen than for those with a microbiologically confirmed viral aetiology (5 [interquartile range (IQR) 3-8] vs. 3 [IQR 2-5]; p < 0.001). Using no doses of dexamethasone as a reference, the weighted OR for an unfavourable outcome were 0.55 (95% CI, 0.29-1.07) for 1-2 doses, 1.13 (95% CI, 0.67-1.89) for 3-4 doses, and 1.43 (95% CI, 0.77-2.64) for ≥5 doses. In the subgroup of enteroviral meningitis, the weighted OR was 3.08 (95% CI, 1.36-6.94) for ≥5 doses, but decreased to 2.35 (95% CI, 0.65-8.40) when the reference group was restricted to patients treated with antibiotics for suspected bacterial meningitis.

Discussion: This study showed no dose-dependent association between dexamethasone and an unfavourable outcome in patients with viral meningitis. In enteroviral meningitis, ≥5 doses were associated with an increased risk of an unfavourable outcome. However, sensitivity analysis indicated that the association was affected by unmeasured or residual confounding by severity.

Objectives: The aim of this study was to determine predictors for helminthiasis among travellers and migrants with eosinophilia for which a visit to tropical regions or endemic regions for common helminthiasis had been registered.

Methods: A retrospective cohort study was performed using electronic health records of 23 905 patients with eosinophilia (January 2011-August 2021) at Karolinska University Hospital, Stockholm, including patients tested for helminthiasis with a registered stay in a helminth endemic region. Outcomes were diagnosis of any helminthiasis and diagnosis of schistosomiasis and strongyloidiasis. Multivariable logistic regression was used to assess associations between potential predictors and helminthiases with a backwards stepwise elimination approach until a predictive model was reached in which each variable had a p value < 0.15.

Results: Of 1112 eligible patients with eosinophilia and documented stay in endemic regions, 219 (19.7%) had been diagnosed with helminthiasis, most frequently schistosomiasis (n = 95, 43.4%) and strongyloidiasis (n = 64, 29.2%). A stay in Sub-Saharan Africa (SSA) (OR, 8.2; 95% CI, 2.44-27.56), malaise and fatigue (OR 2.65; 95% CI, 0.77-9.09), and high-grade eosinophilia >1500 cells/μL (OR 2.26; 95% CI, 1.54-3.32) were the most important predictors for any helminthiasis (area under the curve [AUC], 0.77; 0.74-0.80). An SSA origin (AUC, 2.97; 1.11-7.95), malaise and fatigue (AUC, 5.48; 1.13-26.63), and high-grade eosinophilia (AUC, 1.53; 0.86-2.71) were predictors for schistosomiasis (AUC, 0.74; 0.70-0.77); whereas SSA origin (AUC, 5.68 (3.04-10.59)), itching symptoms (AUC, 5.05; 1.32-19.36), and high-grade eosinophilia (AUC, 2.42; 1.33-4.41) were predictors for strongyloidiasis (AUC, 0.73; 0.69-0.76).

Discussion: A stay in an endemic region, specifically SSA, having high-grade eosinophilia, and malaise and fatigue were the most important predictors for helminthiasis. Itching was an additional predictor for strongyloidiasis.

Objectives: Significant heterogeneity has been reported in cohort studies evaluating the impact of early oral antiviral treatment on preventing postacute sequelae after COVID-19. We evaluated the impact of early nirmatrelvir/ritonavir on risk of postacute cardiovascular, neurological, respiratory, and autoimmune diagnoses, as well as postacute symptoms amongst older Singaporeans.

Methods: National COVID-19 registries and healthcare claims databases were used to construct a retrospective population-based cohort enrolling all Singaporeans aged ≥60 years diagnosed with SARS-CoV-2 infection in primary care during Omicron transmission (18 March 2022-4 August 2023). The cohort was divided into nirmatrelvir/ritonavir-treated and untreated groups. Between-group differences in baseline characteristics were adjusted using overlap weighting. Risks of postacute cardiovascular, neurological, respiratory, and autoimmune diagnoses and postacute symptoms (31-180 days) after SARS-CoV-2 infection were contrasted in treated/untreated groups using competing risks regressions (adjusted for demographics/vaccination status/comorbidities).

Results: A total of 188 532 older Singaporeans were included; 5.8% (10 905/188 532) received nirmatrelvir/ritonavir. No significantly decreased risk of postacute sequelae (any sequelae: adjusted hazards ratio [aHR], 1.06; 0.94-1.19; cardiovascular sequelae: aHR, 1.01; 0.83-1.24; neurological sequelae: aHR, 1.09; 0.95-1.27; respiratory sequelae: aHR, 1.14; 0.84-1.55; autoimmune sequelae: aHR, 0.76; 0.53-1.09; or any postacute symptom: aHR, 0.97; 0.80-1.18) was observed up to 180 days post-infection in nirmatrelvir/ritonavir-treated individuals vs. untreated cases. Across all vaccination and age subgroups, no significantly decreased risk of any postacute diagnosis/symptom or any cardiovascular, neurological, respiratory, and autoimmune complications up to 180 days post-infection was observed.

Discussion: Early outpatient receipt of nirmatrelvir/ritonavir did not significantly reduce risk of postacute cardiovascular, neurological, respiratory, and autoimmune sequelae or the risk of postacute symptoms in a boosted cohort of older Singaporeans.

Objectives: The pathogen of community-acquired pneumonia (CAP) in children is typically uncertain during initial treatment, leading to systematic empiric antibiotic use. This study investigates if having rapid multiplex PCR results in the emergency department (ED) improves empiric treatment.

Methods: OPTIPAC, a French multicentre study (2016-2018), enrolled patients consulting for CAP at the paediatric ED in 11 centres. Patients were randomized to either receive a multiplex PCR test plus usual care or usual care alone and followed for 15 days. The primary outcome was the appropriateness of initial antimicrobial management, determined by a blinded committee.

Results: Of the 499 randomized patients, 248 were tested with the multiplex PCR. Appropriateness of the antibiotic treatment was higher in the PCR group (168/245, 68.6% vs. 120/249, 48.2%; Relative risk 1.42 [1.22-1.66]; p < 0.0001), chiefly by reducing unnecessary antibiotics in viral pneumonia (RR 3.29 [2.20-4.90]). No adverse events were identified.

Discussion: The multiplex PCR assay result at the ED improves paediatric CAP's antimicrobial stewardship, by both reducing antibiotic prescriptions and enhancing treatment appropriateness.

Objectives: Simnotrelvir is a small-molecule highly specific 3C-like protease inhibitor for anti-SARS-CoV-2 and was approved as a combination drug with ritonavir (simnotrelvir/ritonavir) in China. Simnotrelvir is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), and a weak inhibitor of CYP3A. Ritonavir is a substrate and inhibitor of CYP3A and an inhibitor of P-gp. Hence, the drug-drug interaction potential of simnotrelvir/ritonavir should be investigated.

Methods: This drug-drug interaction study was an open-label, fixed-sequence, two-period phase I clinical trial in Chinese healthy adult subjects, divided into three cohorts, including simnotrelvir/ritonavir co-administrated with a strong CYP3A and P-gp inhibitor (itraconazole) and inducer (rifampicin), and with a specific CYP3A substrate (midazolam).

Results: The results demonstrated that compared with administration of simnotrelvir/ritonavir alone, the co-administration with itraconazole increased the geometric least-square mean ratio (GMR) of the expose (area under the plasma concentration-time curve from time zero to the lowest detectable plasma concentration [AUC_0-t]) of simnotrelvir by 25% (GMR 125%, 90% CI 114-137%), whereas co-administration with rifampicin significantly decreased the AUC_0-t of simnotrelvir by 81.5% (GMR 18.5%, 90% CI 16.4-20.9%). Notably, simnotrelvir/ritonavir increased the AUC_0-t of midazolam by 16.69-fold (GMR 1769%, 90% CI 1551-2018%). The co-administration of simnotrelvir/ritonavir and rifampicin caused the increased amount and severity of treatment-emergent adverse events, especially hepatotoxicity.

Discussion: The co-administration of simnotrelvir/ritonavir with CYP3A and P-gp inhibitors can be safely used, whereas the co-administration with CYP3A and P-gp strong inducer should be avoided to minimize the risk of under-exposure. Co-administration of midazolam with simnotrelvir/ritonavir increased systemic exposure of midazolam.

Clinicaltrials: gov Identifier: NCT05665647.