Antecedent Carbapenem Exposure as a Risk Factor for Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae and Carbapenemase-Producing Enterobacteriaceae.

Carbapenem-resistant Enterobacteriaceae (CRE) can be mechanistically classified into carbapenemase-producing Enterobacteriaceae (CPE) and non-carbapenemase-producing carbapenem nonsusceptible Enterobacteriaceae (NCPCRE). We sought to investigate the effect of antecedent carbapenem exposure as a risk factor for NCPCRE versus CPE. Among all patients with CRE colonization and infection, we conducted a case-control study comparing patients with NCPCRE (cases) and patients with CPE (controls). The presence of carbapenemases was investigated with phenotypic tests followed by PCR for predominant carbapenemase genes. We included 843 unique patients with first-episode CRE, including 387 (45.9%) NCPCRE and 456 (54.1%) CPE. The resistance genes detected in CPEs were blaNDM (42.8%), blaKPC (38.4%), and blaOXA-48-like (12.1%). After adjusting for confounders and clustering at the institutional level, the odds of prior 30-day carbapenem exposure was three times higher among NCPCRE than CPE patients (adjusted odds ratio [aOR], 3.48; 95% confidence interval [CI], 2.39 to 5.09; P < 0.001). The odds of prior carbapenem exposure and NCPCRE detection persisted in stratified analyses by Enterobacteriaceae species (Klebsiella pneumoniae and Escherichia coli) and carbapenemase gene (blaNDM and blaKPC). CPE was associated with male gender (aOR, 1.45; 95% CI, 1.07 to 1.97; P = 0.02), intensive care unit stay (aOR, 1.84; 95% CI, 1.24 to 2.74; P = 0.003), and hospitalization in the preceding 1 year (aOR, 1.42; 95% CI, 1.01 to 2.02; P = 0.05). In a large nationwide study, antecedent carbapenem exposure was a significant risk factor for NCPCRE versus CPE, suggesting a differential effect of antibiotic selection pressure.

Cerebellar Stroke in a COVID-19 Infected Patient. a Case Report.

BACKGROUND: Recent studies have reported that COVID-19 infected patients with stroke, who were often in the older age group, had a higher incidence of vascular risk factors, and more severe infection related respiratory symptoms. These observations provided little evidence to suggest that COVID-19 infection is a potential causative factor for stroke. This report describes a young patient with a cerebellar stroke secondary to COVID-19 infection. CASE PRESENTATION: A 45-year old male presented at a hospital, reporting a two-day history of headache, vertigo, persistent vomiting, and unsteady gait. Physical examination revealed gaze-evoked nystagmus on extraocular movement testing, left-sided dysmetria and dysdiadochokinesia. He was diagnosed with a left cerebellar stroke. An external ventricular drain was inserted, and sub-occipital craniectomy was performed to manage the effects of elevated intracranial pressure due to the extent of oedema secondary to the infarct. He also underwent screening for the COVID-19 infection, which was positive on SARS-COV-2 polymerase chain reaction testing of his endotracheal aspirate. Blood and cerebrospinal fluid samples were negative. After the surgery, the patient developed atrial fibrillation and had prolonged vomiting symptoms, but these resolved eventually with symptomatic treatment. He was started on aspirin and statin therapy, but anticoagulation was withheld due to bleeding concerns. The external ventricular drain was removed nine days after the surgery. He continued with active rehabilitation. CONCLUSIONS: Young patients with COVID-19 infection may be more susceptible to stroke, even in the absence of risk factors. Standard treatment with aspirin and statins remains essential in the management of COVID-19 related stroke. Anticoagulation for secondary prevention in those with atrial fibrillation should not be routine and has to be carefully evaluated for its benefits compared to the potential harms of increased bleeding associated with COVID-19 infection.

A Dynamic Immune Response Shapes COVID-19 Progression.

The inflammatory response to SARS-coronavirus-2 (SARS-CoV-2) infection is thought to underpin COVID-19 pathogenesis. We conducted daily transcriptomic profiling of three COVID-19 cases and found that the early immune response in COVID-19 patients is highly dynamic. Patient throat swabs were tested daily for SARS-CoV-2, with the virus persisting for 3 to 4 weeks in all three patients. Cytokine analyses of whole blood revealed increased cytokine expression in the single most severe case. However, most inflammatory gene expression peaked after respiratory function nadir, except expression in the IL1 pathway. Parallel analyses of CD4 and CD8 expression suggested that the pro-inflammatory response may be intertwined with T cell activation that could exacerbate disease or prolong the infection. Collectively, these findings hint at the possibility that IL1 and related pro-inflammatory pathways may be prognostic and serve as therapeutic targets for COVID-19. This work may also guide future studies to illuminate COVID-19 pathogenesis and develop host-directed therapies.