Phenotypical and molecular assessment of the virulence potential of KPC-3-producing Klebsiella pneumoniae ST392 clinical isolates.

Klebsiella pneumoniae is a Gram-negative bacterium of clinical importance, due to its resistance to several antibiotic classes. We have identified 4 clinical isolates of K. pneumoniae sequence type (ST) 392 KPC-3-producing strains from patients at the Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (IRCCS-ISMETT), a Southern Italian transplantation health facility, during a routine surveillance for carbapenemase-producing Enterobacterales from in-house clinical samples. Since those were among, to the best of our knowledge, the first KPC-producing K. pneumoniae ST392 isolated in Europe, we assessed their virulence potential, to understand if this particular ST can become an endemic clinical threat. ST392 isolates were investigated to assess their virulence potential, namely resistance to human sera, formation of abiotic biofilms, adhesion to biotic surfaces, exopolysaccharide production and in vivo pathogenesis in the wax moth Galleria mellonella animal model. ST392-belonging strains were highly resistant to human sera. These strains also have a high capacity to form abiotic biofilms and high levels of adhesion to the human epithelial colorectal adenocarcinoma HT-29 cell line. An increase of transcriptional levels of genes involved in serum resistance (aroE and traT) and adhesion (pgaA) was observed when compared with the Klebsiella quasipneumoniae subsp. similipneumoniae strain ATCC 700603 reference strain. Infection of G. mellonella larvae with ST392 clinical isolates showed that the latter were not highly pathogenic in this model. Together, our results indicate that ST392 isolates have the potential to become a strain of clinical relevance, especially in health settings where patients are immunosuppressed, e.g., transplant recipients.

How can we optimise antifungal use in a solid organ transplant centre? Local epidemiology and antifungal stewardship implementation: A single-centre study.

PURPOSE: We aimed to implement and to assess the impact of the antifungal stewardship programme (AFSp) on prescription appropriateness of antifungals, management and outcomes of candidaemia patients, and antifungal consumption and costs at our solid organ transplant (SOT) institute. METHODS: Local epidemiology of invasive fungal infections (IFIs) from 2009 to 2017 was analysed in order to prepare an effective AFSp, implemented in January 2018. It included suspension of empirical antifungal prescriptions after 72 hours (antifungal time-out), automated alert and infectious disease (ID) consult for empirical prescriptions and for every patient with IFI, and indication for step-down to oral fluconazole when possible. We used process measures and results measures to assess the effects of the implemented programme. RESULTS: The ASFp led to significant improvements in selection of the appropriate antifungal (40.5% in pre-AFS vs 78.6% in post-AFS), correct dosing (51.2% vs 79.8%), correct length of treatment (55.9% vs 75%) and better management of patients with candidaemia. Analysis of prescribed empirical antifungal revealed that defined daily doses (DDDs) per 100 patient days decreased by 36.7% in 2018 compared to the average of pre-AFSp period, with important savings in costs. CONCLUSION: This AFSp led to a better use of antifungal drugs in terms of appropriateness and consumption, with stable clinical and microbiological outcomes in patients with IFI.

Posttraumatic epilepsy: neuroradiologic and neuropsychological assessment of long-term outcome.

PURPOSE: We sought to detect the incidence and the risk factors of posttraumatic epilepsy (PTE) in rehabilitation patients; to define the influence of PTE for late clinical and functional outcome; and to assess the cognitive and behavioral features of the patients with PTE. METHODS: Patients were examined with (a) cognitive and behavioral examinations, which included a clinical interview and psychometric tests performed by an expert clinical psychologist; (b) single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI); and (c) functional evaluation including the Glasgow Outcome Scale (GOS) and the Functional Independence Measure (FIM). RESULTS: Of the 143 patients examined in this study, in 27 (19%), seizures developed after a mean time from trauma of 11.9 +/- 8.6 months. The occurrence of PTE was significantly correlated with the hypoperfusion in temporal lobes (p < 0.004), the degree of hydrocephalus (p < 0.04), the evidence of intracerebral hematoma (p < 0.01), and operative brain injury (p < 0.001). Patients with epilepsy showed a significantly higher incidence of personality disorders than did patients without epilepsy. The uninhibited behavior, irritability, and agitated and aggressive behavior were significantly more frequent and severe in PTE patients. The psychometric tests intended to explore memory, language, intelligence, attention, and spatial cognition did not show any significant difference between those with and without epilepsy. PTE also was significantly correlated with a worse functional outcome 1 year after the trauma. CONCLUSIONS: The degrees of hydrocephalus and of hypoperfusion in the temporal lobes are significant risk factors for late PTE. Another main finding of our study is the absence of influence of epilepsy on cognitive disorders; its influence on neurobehavioral disorders and functional outcome is discussed.