Infection最新文献

Purpose: Isavuconazole is effective against invasive aspergillosis (IA) and mucormycosis (IM) and may improve clinical outcomes compared to alternative antifungal treatments. However, real-world evidence regarding its clinical use and the health economic burden of inpatient treatment for IA and IM of patients with haematological malignancies remains limited.

Methods: A retrospective, matched, multicentre cohort study was conducted in six German tertiary care centres. The study included adults with haematological or oncological diseases who were diagnosed with proven, probable, or possible IA or IM. We compared clinical and health economic outcomes under first-line treatment initiated with isavuconazole (case group) vs. liposomal amphotericin B (L-AmB) and/or voriconazole (control group) between 2016 and 2021. A micro-costing approach was used to assess direct treatment costs.

Results: We included 198 patients (99 per group), most with a probable or possible classification. Median length of hospital stay was 44 days (interquartile range [IQR] 27-74) in the isavuconazole group and 39 days (IQR 26-56) in the control group (p = 0.285). All-cause mortality rates were 29% and 31% (p = 0.530), with fungal-related deaths occurring in 21% (n = 6) and 23% (n = 7, p = 0.862), respectively. Mean antifungal drug acquisition and overall treatment costs were significantly higher in the isavuconazole group (€22,389 vs. €12,801, p = 0.003; €49,042 vs. €39,369, p = 0.030, respectively), while mean hospitalisation costs were comparable (€28,570 vs. €31,160, p = 0.406).

Conclusion: Our real-world analysis confirmed that first-line treatment initiated with isavuconazole resulted in clinical outcomes equivalent to those of L-AmB and/or voriconazole in patients with IA or IM. However, treatment costs during the in-patient stay were higher with isavuconazole.

Purpose: Fluconazole is the recommended step-down therapy from echinocandins for fluconazole-susceptible Candida spp in critically ill patients with invasive candidiasis. However, standard fluconazole dosing does not achieve adequate exposure in these patients. We aimed to identify factors impacting fluconazole pharmacokinetic-pharmacodynamic (PKPD) target attainment and provide a dosing regimen ensuring adequate target attainment in critically ill patients.

Methods: A population pharmacokinetics study (popPK) was conducted, combining fluconazole concentration data from eight studies. We used multiple imputation to handle missing covariate data, and Monte Carlo simulations to identify a dosing regimen with at least 90% probability of PKPD target attainment (PTA) in every patient. The PKPD target is the 24-hour area under the unbound concentration-time curve over the minimum inhibitory concentration of 100.

Results: Data from 177 critically ill patients were included. A two-compartment popPK model with linear elimination described the data best. Continuous renal replacement therapy (CRRT) status, estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation, and total body weight were statistically significant covariates. However, with standard dosing, only CRRT status and total body weight were clinically relevant, as PTA dropped below 90% for all patients on CRRT, and for patients off-CRRT above 60 kg. A weight-based loading dose and flat maintenance doses of 400 mg (off-CRRT) and 800 mg (CRRT) predicted ≥ 90% PTA across the weight range.

Conclusion: We have developed a fluconazole dosing regimen, stratified by weight and CRRT status, that may achieve adequate PTA in critically ill patients. External validation is awaited.

Introduction: Tuberculosis (TB) remains a significant global health issue, with extrapulmonary manifestations accounting for a notable proportion of cases. Perianal tuberculosis, however, is a rare presentation of TB, often leading to delayed diagnosis due to its nonspecific symptoms and similarity to other perianal diseases.

Methods: We present a case of perianal TB as primary manifestation leading to the diagnosis of simultaneous pulmonary TB, and a review of the literature based on a search in Medline.

Results: A 47-year-old male presented with perianal pain and purulent discharge. Histopathological examination and PCR analysis following surgical intervention confirmed the diagnosis of perianal TB. Chest imaging revealed nodular and cavitary lung lesions, indicating active pulmonary TB. The patient was initiated on a 9-month anti-tuberculosis treatment. Contact tracing identified latent TB infections among two close family members. Our literature search identified 59 relevant publications comprising 195 cases. The majority of the patients were male (88%), with a median age of 42 years, and originated from high prevalence regions. In many instances, diagnosis was delayed, with a mean duration of approximately two years from symptom onset to confirmation (median 6 month). Pulmonary tuberculosis was concurrently present in one third of the cases.

Conclusion: Diagnosis of perianal TB is often delayed due to its rarity and nonspecific clinical presentation. TB must be considered in the differential diagnosis of ulcerative, fistulous and abscess-forming lesions of the perianal area, especially if recurrent, and in patients originating from high prevalence countries of TB. In many cases, further diagnostic evaluations reveal simultaneous pulmonary tuberculosis, underscoring the importance of a comprehensive diagnostic approach. From a clinical and public health perspective, early diagnosis and prompt initiation of treatment are essential to prevent disease progression and transmission.

Introduction: The global resurgence of scarlet fever and invasive group A Streptococcus (GAS) infections has been noted over the past decade. In East Asia, specifically in Hong Kong and China, emm12 isolates that acquired prophage ΦHKU.vir, which carried SSA, SpeC, and Spd1 exotoxins, were over-presented in scarlet fever cases. The prevalence of ssa-positive emm12 isolates was increased significantly in Taiwan; however, it remains unclear whether this increase is mediated by the horizontal transfer of ΦHKU.vir homologs or the expansion of Hong Kong scarlet fever-associated emm12 isolates.

Materials and methods: This study included 240 non-emm1 isolates in Taiwan during 2009-2023. The genome and prophage sequences of clinical isolates were analyzed by whole genome sequencing.

Results: The prophages carried ssa, speC, and spd1 in Taiwan emm12 isolates shared high nucleotide sequence identity with ΦHKU.vir. All analyzed emm12 isolates in Taiwan were phylogenetically closely related to Hong Kong emm12 isolates, suggesting that Taiwan ssa-positive emm12 isolates shared a common origin with those from Hong Kong. This study further identified ΦHKU.vir homologs in emm90 and acapsular emm89 isolates. Although the acquisition of ΦHKU.vir is related to the expansion of emm12 isolates in Hong Kong, this study suggests that the prophage exotoxin SSA did not have significant roles in enhancing bacterial cytotoxicity and intracelluar survival of the acapsular emm89 strains.

Conclusions: The acquisition of prophages is important for the evolution of GAS. Monitoring the expansion of ΦHKU.vir in non-emm1/emm12 isolates is essential, as studying its impact on GAS pathogenicity will help in preventing and controlling GAS infections.

Objectives: For the past five years, COVID-19 has not only been a priority for health planning but also a hotspot for clinical research. Yet, the weight of the worldwide COVID-19 pandemic arises from the critical phase consequences due to the onset of acute disease, associated containment measures, and documented ongoing disabling symptoms. Investigating the global longitudinal effects on children and adolescents will inform future health directives tailored to this population's needs. This review aimed to report the spectrum of persistent neurological sequelae in children and adolescents following SARS-CoV-2 infection.

Methods: Hence, we conducted a scoping review following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). We included the peer-reviewed articles from PubMed, Google Scholar, Web of Science, Cochrane Library, and WHO COVID database to identify relevant literature on long-COVID-19 neurological signs/symptoms among children and adolescents. The search covered the period between September 2020 and September 2024.

Results: The results of our analysis of 33 studies found long-COVID-19-related neurological signs/symptoms were predominantly: pain and sensory problems (N = 74,612/91,543; 81.5%), followed by sleep disturbances (N = 14,630/91,543; 15.9%), and cognitive difficulties (N = 2274/91,543; 2.4%). The global prevalence of long COVID-19 neurological signs/symptoms was estimated between 0.4% (20/5032; 95% CI = 2.1-3%) and 34% (27/79) based on data obtained through online questionnaire; while it varied between 1.8% (4/215) and 83.14% (74/89; 95%CI =   -  0.12; 0.30) based on patient assessment. Long-COVID-19-related neurological signs/symptoms were more common in the 11-16 age group. Children with immunocompetent profiles were at higher risk of developing long-COVID-19-related neurological signs/symptoms.

Conclusion: Our results demonstrate a considerable burden of COVID-19-related persistent neurological signs/symptoms in children and adolescents, which should be taken into consideration in healthcare decision-making.

Purpose: The study aimed to compare the clinical outcomes and safety of trimethoprim/sulfamethoxazole (TMP/SMX) versus levofloxacin monotherapy in patients with monomicrobial Stenotrophomonas maltophilia (S. maltophilia) bacteremia.

Methods: We conducted a retrospective cohort study of adult inpatients with monomicrobial S. maltophilia bacteremia at a tertiary medical center in Taiwan from January 2004 to June 2025. Patients were divided into two groups for comparison based on antibiotic treatment: TMP/SMX and levofloxacin monotherapy. Primary outcome was 30-day mortality. Secondary outcomes included in-hospital mortality, clinical response, microbiological eradication, non-susceptible strains emergence, recurrent bacteremia, and adverse drug reactions. Multivariable logistic regression and propensity score analysis were performed using inverse probability of treatment weighting (IPTW).

Results: Among 226 patients, 129 received levofloxacin and 97 received TMP/SMX. The levofloxacin-treated group was associated with lower 30-day mortality (17.8% vs. 36.1%, p = 0.002) in the primary analysis. In the multivariable logistic regression model, levofloxacin use was independently associated with improved outcomes (p = 0.047). Similarly, in the IPTW analysis, levofloxacin use remained a factor of lower 30-day mortality (p = 0.026). Additionally, microbiological eradication, emergence of non-susceptible strains, and recurrent bacteremia were comparable between the treatment groups, while adverse events were significantly less frequent in patients treated with levofloxacin (3.1% vs. 25.8%, p < 0.001).

Conclusions: Levofloxacin appeared to be more effective and safer than TMP/SMX in this retrospective analysis; however, this interpretation should be made with caution given the observational nature of the study. Further randomized clinical trials are warranted to validate these findings.