Whole Genome Sequence Dataset of Mycobacterium tuberculosis Strains from Patients of Campania Region.

Tuberculosis (TB) is one of the deadliest infectious disorders in the world. To effectively TB manage, an essential step is to gain insight into the lineage of Mycobacterium tuberculosis (MTB) and the distribution of drug resistance. Although the Campania region is declared a cluster area for the infection, to contribute to the effort to understand TB evolution and transmission, still poorly known, we have generated a dataset of 159 genomes of MTB strains, from Campania region collected during 2018-2021, obtained from the analysis of whole genome sequence. The results show that the most frequent MTB lineage is the 4 according for 129 strains (81.11%). Regarding drug resistance, 139 strains (87.4%) were classified as multi susceptible, while the remaining 20 (12.58%) showed drug resistance. Among the drug-resistance strains, 8 were isoniazid-resistant MTB, 4 multidrug-resistant MTB, while only one was classified as pre-extensively drug-resistant MTB. This dataset expands the existing available knowledge on drug resistance and evolution of MTB, contributing to further TB-related genomics studies to improve the management of this disease.

Fosfomycin-meropenem synergistic combination against NDM carbapenemase-producing Klebsiella pneumoniae strains.

Carbapenemase-producing Enterobacteriaceae (CPE) are an increasing threat to global public health. Treatment of CPE isolates, like New Delhi metallo-ß-lactamase (NDM), is limited and often necessitates combination therapies. The aim of this study was to evaluate the synergistic meropenem/fosfomycin combination against K.pneumoniae-producing NDM isolates. Fosfomycin/meropenem, fosfomycin/colistin and meropenem/colistin were tested alone and in combination, using e-test and time-kill assay against 20 clinical carbapenemase-producing K. pneumonia (CPKp NDM) isolates collected from September 2022 to December 2022. K. pneumoniae strains were resistant to meropenem, ceftazidime/avibactam and ceftolozano/tazobactam, 75% and 80% of isolates were susceptible for cefiderocol and for colistin respectively. Fosfomycin/meropenem combination was synergic in 95% (n=19) strains. Fosfomycin/colistin and colistin/meropenem combination showed only 10% synergistic combination strains. In 16 isolates (80%) indifference action for fosfomycin/colistin and colistin/meropenem was reported. For 0.8% of CpKP NDM isolates colistin/meropenem and fosfomycin/colistin combinations found to be antagonistic. In this study, time kill assay showed combination therapies action versus K.pneumoniae metallo-b-lactamase producing (NDM) strains and confirmed the synergistic action of fosfomycin/meropenem combination. In vitro synergy testing should be routinely performed in multidrug resistance infections and combo therapies can be used as a possible alternative in targeted patients with the goal of reducing overall antibiotic costs.

Pathogens distribution and antimicrobial resistance pattern of blood stream infections in Southern Italian hospital, 2016-2021 surveillance.

Bloodstream infections (BSIs) monitoring and antibiotic susceptibility assumes a priority relevance to guide antibiotic treatment strategies and prevention programs. The study aims to identify the most common causative agents of BSIs, seasonal distribution and variation of antimicrobial susceptibility rates during a 6-year period in a in a Level II EAD Southern Italian Hospital. The study was conducted from 2016 to 2021 at Hospital of National Relevance (AORN) Sant'Anna and San Sebastiano, Caserta, Campania Region in Italy. BSIs Gram positive causative pathogens were S. aureus and Enterococci; Gram negative pathogens were E. coli, K. pneumoniae, P. aeruginosa and A. baumannii. Seasonal distribution showed the main incidence in April-June for Gram positive BSIs pathogens and in July-September months for Gram negative. Antimicrobial susceptibility fluctuations rates from 2016-2018 to 2019-2021 highlighted a significant decrease in S. aureus oxacillin resistance rates. Enterococci incremented resistance was reported for gentamicin. Gram negative pathogens antimicrobial susceptibility revealed decreased carbapenem-resistance rates for K. pneumoniae (-21.5%) and P. aeruginosa (-19.7%). A. baumannii colistin resistance had a significant increase in 2019-2021. K. pneumoniae and E. coli isolates showed decreased trend of extended-spectrum -lactamase-producing (ESBL) and carbapenem-resistant (CRE) resistance profiles. Our finding reflects the success of our Istitution regarding antimicrobial stewardship program and highlights the need to know the trend of antimicrobial resistance characterization focus on local pathogens' profile. In this way, in conjunction with infection control strategies, il could be possible to constantly reduce the spread of Multi Drug Resistant organisms.

Profile of Co-Infection Prevalence and Antibiotics Use among COVID-19 Patients.

Bacterial co-infection in COVID-19 patients significantly contributes to the worsening of the prognosis based on morbidity and mortality. Information on the co-infection profile in such patients could help to optimize treatment. The purpose of this study was to describe bacterial co-infections associated with microbiological, clinical, and laboratory data to reduce or avoid a secondary infection. A retrospective cohort study was conducted at Sant'Anna and San Sebastiano Hospital from January 2020 to December 2021. Bacterial co-infection was detected in 14.3% of the COVID-19-positive patients. The laboratory findings on admission showed significant alterations in the median D-dimer, C-reactive protein, interleukin-6, and lactate dehydrogenase values compared to normal values. All inflammatory markers were significantly elevated. The most common pathogens isolated from blood cultures were E. faecalis and S. aureus. Instead, the high prevalence of respiratory tract infections in the COVID-19 patients was caused by P. aeruginosa (41%). In our study, 220 (82.4%) of the COVID-19 patients received antimicrobial treatment. Aminoglycosides and ß-lactams/ß-lactamase inhibitors showed the highest resistance rates. Our results showed that older age, underlying conditions, and abnormal laboratory parameters can be risk factors for co-infection in COVID-19 patients. The antibiotic susceptibility profile of bacterial pathogen infection provides evidence on the importance, for the clinicians, to rationalize and individualize antibiotic usage.

Diagnostic and infection control strategies for Clostridioides difficile infections in a setting of high antimicrobial resistance prevalence.

Clostridioides difficile (CD) is a major nosocomial pathogen and the leading cause of antibiotic-associated diarrhoea. In light of the strong association between antimicrobial use and CD infections (CDI), it may be hypothesised that areas at higher prevalence of antimicrobial resistance, like the region of Campania in southern Italy, could also have a higher rate of CDI. In this multicentre, region-based, prospective study, we analysed such issues, exploiting CDI incidence data collected from local hospitals. In 2016, the Italian National Centre for Disease Control supported a project involving three Italian regions: Friuli Venezia Giulia, Lazio and Campania. In Campania, a network of 49 hospitals willing to participate in the project was created. The project consisted of two phases: a survey on practice patterns concerning CDI and an epidemiological surveillance study. We identified a stringent need to improve awareness about CDI among the regional health-care community, as a widespread lack of surveillance programmes for CDI control was observed (existing in only 40% of participating facilities). Moreover, almost half of the participating hospitals (n=16, 43%) had no standardised procedures or protocols to control and prevent CDI. In the second phase of the study, we collected data of CDI cases during a six-month surveillance programme. In all, 87 CDI cases were observed, for a total of 903,334 patient bed-days and 122,988 admissions. According to the above data, CDI incidence was 0.96 cases/10000 patient bed-days, much lower than expected based on prior studies conducted elsewhere. The results of our study suggest CDI remains a rather neglected clinical issue in Campania. Despite a high burden of antimicrobial resistance and antimicrobial use in our geographic setting, we observed a very low incidence of CDI. Such a low incidence could be explained by underdiagnosis, but could also be related to actual diet, the lower patient age or the specific genetic background. However, further studies are warranted to either confirm or rebut the above hypotheses.

Functional dissection of the Drosophila Kallmann's syndrome protein DmKal-1.

BACKGROUND: Anosmin-1, the protein implicated in the X-linked Kallmann's syndrome, plays a role in axon outgrowth and branching but also in epithelial morphogenesis. The molecular mechanism of its action is, however, widely unknown. Anosmin-1 is an extracellular protein which contains a cysteine-rich region, a whey acidic protein (WAP) domain homologous to some serine protease inhibitors, and four fibronectin-like type III (FnIII) repeats. Drosophila melanogaster Kal-1 (DmKal-1) has the same protein structure with minor differences, the most important of which is the presence of only two FnIII repeats and a C-terminal region showing a low similarity with the third and the fourth human FnIII repeats. We present a structure-function analysis of the different DmKal-1 domains, including a predicted heparan-sulfate binding site. RESULTS: This study was performed overexpressing wild type DmKal-1 and a series of deletion and point mutation proteins in two different tissues: the cephalopharyngeal skeleton of the embryo and the wing disc. The overexpression of DmKal-1 in the cephalopharyngeal skeleton induced dosage-sensitive structural defects, and we used these phenotypes to perform a structure-function dissection of the protein domains. The reproduction of two deletions found in Kallmann's Syndrome patients determined a complete loss of function, whereas point mutations induced only minor alterations in the activity of the protein. Overexpression of the mutant proteins in the wing disc reveals that the functional relevance of the different DmKal-1 domains is dependent on the extracellular context. CONCLUSION: We suggest that the role played by the various protein domains differs in different extracellular contexts. This might explain why the same mutation analyzed in different tissues or in different cell culture lines often gives opposite phenotypes. These analyses also suggest that the FnIII repeats have a main and specific role, while the WAP domain might have only a modulator role, strictly connected to that of the fibronectins.