Clinical Microbiology and Infection最新文献

Background: Diagnosing infectious encephalitis can be challenging as it can be caused by a wide range of pathogens, with viruses being the most common cause. In a substantial number of patients, no pathogen is identified despite a clinical diagnosis of infectious encephalitis. Recent advancements in diagnostic testing have introduced new methods to address this diagnostic challenge and improve pathogen detection.

Objectives: The objective of this study is to provide a comprehensive clinical approach for diagnosing infectious encephalitis and explore novel diagnostic methods.

Sources: We searched PubMed to identify relevant literature on diagnosing encephalitis in English up to 1 September 2024, as well as included articles known by the authors.

Content: Clinical characteristics may suggest a specific cause of infectious encephalitis, but are insufficient to guide treatment decisions. Therefore, cerebrospinal fluid (CSF) examination remains the cornerstone of the diagnostic process, with CSF leucocyte count being the most reliable predictor for central nervous system infections. CSF features can be normal, however, in a proportion of patients presenting with infectious encephalitis. A definite diagnosis of infectious encephalitis is established by microbiological or histopathological tests in ∼50% of patients. Additional investigations, including neuroimaging or electroencephalography, can provide evidence for encephalitis or help to identify alternate conditions, although their role is primarily supportive. Emerging diagnostic techniques, including next-generation sequencing metagenomics and unbiased serology (Phage ImmunoPrecipitation Sequencing), have the potential to increase the proportion of patients with a confirmed diagnosis. However, these techniques are not yet practical because of their complex analysis, long turnaround times and high costs.

Implications: Microbiological confirmation is paramount in the diagnosis of infectious encephalitis, but it is currently established in about half of cases. Although novel techniques show promise to increase the proportion of cause-specific diagnoses, they are not yet suitable for routine use. This highlights the ongoing need for advancements in diagnostic methods.

Objectives: Semi-automated surveillance systems save time compared with traditional manual methods, particularly for non-ventilator hospital-acquired pneumonia (nvHAP), a nosocomial infection which can affect all non-intubated patients. In semi-automated surveillance, a computerized algorithm selects patients with high probability (i.e. "at risk") for subsequent manual confirmation. This study aimed to evaluate the performance of several single indicators and algorithms to preselect patients at risk for nvHAP.

Methods: Single nvHAP indicators, identified based on literature, expert opinion and data availability, were combined to simple and complex algorithms. Both single indicators and algorithms were applied on a patient cohort of 157 902 patients, including 947 patients with nvHAP according to our reference standard, i.e. validated semi-automated nvHAP surveillance system plus the manual surveillance of patients with hospital-acquired pneumonia discharge diagnostic codes. Performance characteristics like sensitivity, workload reduction, and number of patients needed to be screened to detect one case of nvHAP were assessed.

Results: Compared with the reference standard, single indicators had a sensitivity ranging from 35.1% (332/947) (oxygen desaturation) to 99.7% (944/947) (radiologic procedure). The workload reduction varied from 57.3% (90 505/157 902) (length of hospital stay >5 days) to 98.4% (155 453/157 902) (ICD-10 discharge diagnostic code). The highest workload reduction was found in complex algorithms, e.g. the combination "radiologic procedure including full text AND temporally related abnormal white blood count or fever AND antimicrobials AND C-reactive protein AND decreased oxygenation AND hospital stay ≥5 days AND no intubation" which reduced the number of patients who have to undergo manual review by 96.2% (151 867/157 902), while maintaining a sensitivity of 92% (871/947). The number needed to screen applying this algorithm was 6.4 patients.

Discussion: Several single indicators and algorithms showed a high workload reduction and a sensitivity above the defined threshold of 90%. Our results could assist hospitals or stakeholders of surveillance initiatives in developing algorithms customized to their local conditions.

Objectives: Post-hoc analyses of the MERINO trial highlight the uncertainty associated with establishing piperacillin-tazobactam (PTZ) susceptibility in extended-spectrum beta-lactamase-producing Enterobacterales. Herein, we compare the concordance of susceptibility for PTZ among the VITEK 2, disc diffusion, and Etest with broth microdilution (BMD) as the reference standard.

Methods: Ninety-four consecutive ceftriaxone non-susceptible Escherichia coli and Klebsiella pneumoniae bloodstream isolates were identified from patients at three hospitals in Montréal, Québec. BMD was used as the reference standard against which disc diffusion, VITEK 2 (AST-N391), and Etest susceptibility testing were compared. Errors were categorized as very major (false susceptible), major (false resistant), and minor (other).

Results: Overall, 68/94 (72.3%) of isolates were susceptible to PTZ by BMD. Disc diffusion made no major or very major errors (0%; 97.5% CI: 0-3.8%). The VITEK 2 system had a major error rate of 2.5% (95% CI: 0.003-0.089%) and a very major error rate of 26.7% (95% CI: 0.08-0.55%); however, all isolates with VITEK 2 minimal inhibitory concentrations (MICs) of ≤4 μg/mL were susceptible. Finally, the Etest had a major error rate of 6.3% (95% CI: 0.02-0.14%), but no very major errors. Combining VITEK 2-determined susceptibility with a second test led to an increase in the number of correctly classified susceptible organisms.

Discussion: The VITEK 2 system, and to a lesser extent the Etest, risk major errors. Used alone, the VITEK 2 system also risks very major errors if the estimated MIC is > 4 μg/mL. Combining VITEK 2 with disc diffusion in isolates with an estimated MIC of 8-16 μg/mL could prevent both major and very major errors.

Objectives: To evaluate the effectiveness of ceftaroline vs. vancomycin or daptomycin in the treatment of methicillin-resistant Staphylococcus aureus bloodstream infections (BSIs) (MRSA-BSIs).

Methods: This multicentre retrospective study conducted in 15 Spanish hospitals included data from the first MRSA-BSIs of adult patients between January 2019 and December 2022. The ceftaroline group included patients who received ceftaroline for ≥72 hours within the first week of BSI onset; the standard-of-care (SOC) group included patients who received vancomycin or daptomycin ≥72 hours after BSI onset. Primary outcome was 30-day all-cause mortality; secondary outcomes included 90-day mortality and incidence of adverse events (AEs). Propensity-score matching and Cox proportional hazards analyses were performed.

Results: A total of 429 MRSA-BSIs were included: 133 in the ceftaroline group and 296 in the SOC group. More patients in the ceftaroline group had a Sequential Organ Failure Assessment score >2 (51.1% vs. 36.5%; p < 0.01), complicated BSI (66.2% vs. 42.2%; p < 0.01), infective endocarditis (18.8% vs. 6.4%; p < 0.01) and prescribed in combination treatment (65.4% vs. 11.5%; p < 0.01), with no statistically significant differences in 30-day mortality: 23.3% ceftaroline (95% CI, 16.1-30.5%) vs. 16.2% SOC (95% CI, 12.0-20.4%), p 0.08. There were no statistically significant differences in 90-day mortality (33.1% ceftaroline vs. 26.7% SOC; p 0.17). After propensity-score matching, 105 patients treated with ceftaroline were matched with 105 controls: the 30-day mortality rates were 21.9% and 16.2% (p 0.38). Cox regression analysis of the entire cohort (n = 429) revealed that age (hazard ratio [HR], 1.05; 95% CI, 1.03-1.07) and Sequential Organ Failure Assessment score >2 (HR, 2.34; 95% CI, 1.50-3.65) were associated with 90-day mortality risk, although ceftaroline treatment did not demonstrate a significant effect (HR, 1.00; 95% CI, 0.97-1.02). Incidence of AEs was 12.0% in ceftaroline vs. 4.4% in the SOC group (p < 0.01). Most AEs occurred when ceftaroline was used in combination vs. monotherapy (17.2% vs. 2.2%; p 0.01).

Discussion: Ceftaroline was an effective treatment for MRSA-BSIs but was commonly prescribed in combination showing a higher incidence of AEs.

Background: Encephalitis is a serious condition accompanied by substantial morbidity. Although infections have long been recognized as causes, there has been growing appreciation of autoimmune aetiologies of encephalitis, most notably those associated with anti-neuronal antibodies.

Objectives: This narrative review focuses on points of commonality among clinical features, pathophysiology, and management of infectious and autoimmune encephalitis, while also noting important distinctions.

Sources: I identified studies, comprising research articles and reviews, that provide data on the epidemiology of infectious versus autoimmune encephalitis, and on clinical features that either co-occur or distinguish between them. In addition, I reviewed management practices, preclinical data, and clinical trials on the treatment of infectious and autoimmune encephalitis.

Content: I first discuss the clinical overlap between infectious and autoimmune causes of encephalitis, highlighting features and syndromes that can confound the diagnosis. I next turn to the pathogenic overlap between the two, exemplified by the development of autoimmune encephalitis with antibodies against the N-methyl-D-aspartate receptor following a bout of herpes simplex encephalitis. Finally, I discuss management of infectious and autoimmune encephalitis, focusing on current and future avenues of treatment.

Implications: Although our understanding of causes of infectious and autoimmune encephalitis has improved considerably over the past decade, diagnosis remains challenging given the clinical and pathophysiological overlap between the two. Large multicentre clinical trials are needed to evaluate treatments that target inflammation and potentially benefit both.

Objectives: A post hoc analysis used pooled STRIVE/ReSTORE trial data to determine outcomes with rezafungin versus caspofungin by Candida species and antifungal susceptibility.

Methods: The efficacy and safety of once weekly rezafungin 400/200 mg versus once daily caspofungin 70/50 mg was demonstrated in the randomized, double-blind phase 2 STRIVE (NCT02734862) and phase 3 ReSTORE (NCT03667690) trials involving adults with candidaemia and/or invasive candidiasis. In this analysis, data were pooled for patients with a documented Candida infection within 96 hours of randomization who also received ≥1 dose of study drug. Treatment outcomes were evaluated by Candida species and baseline MICs. Susceptibility was determined using European Committee on Antimicrobial Susceptibility Testing E.Def 7.4 broth microdilution methodology, with Tween 20-supplemented medium for rezafungin.

Results: A total of 294 patients were included (rezafungin: N = 139, caspofungin: N = 155). Susceptibility testing at baseline identified three rezafungin non-susceptible isolates. Day 14 global cure rates were numerically similar between groups for C. albicans (rezafungin: 61.0% [36/59], caspofungin: 65.2% [45/69]) and C. tropicalis (rezafungin: 70.4% [19/27], caspofungin: 63.6% [14/22]), but higher with rezafungin than caspofungin for C. glabrata (rezafungin: 71.1% [27/38], caspofungin: 60.0% [21/35]) and C. parapsilosis (rezafungin: 78.6% [11/44], caspofungin: 55.6% [15/27]). Day 30 all-cause mortality rates were numerically similar between groups for C. albicans (rezafungin: 22.0% [13/59], caspofungin: 18.8% [13/69]) and C. glabrata (rezafungin: 15.8% [6/38], caspofungin: 11.4% [4/35]), but higher with caspofungin than rezafungin for C. tropicalis (rezafungin: 18.5% [5/27], caspofungin: 31.8% [2/22]) and C. parapsilosis (rezafungin: 7.1% [1/14], caspofungin: 29.6% [8/27]). Day 5/14 mycological eradication rates were numerically similar between treatments for C. albicans and C. parapsilosis, but higher with rezafungin for C. glabrata and C. tropicalis. Outcomes by Candida species were not associated with treatment-specific MICs.

Discussion: Rezafungin appears to be an effective treatment for candidaemia/invasive candidiasis irrespective of baseline Candida species.