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.

Characterization of hepatitis virus co-infections in a cohort of immigrants living in southern Italy.

To characterize viral hepatitis co-infections in a cohort of immigrants living in southern Italy. In a prospective multicenter study, all undocumented immigrants and low-income refugees consecutively evaluated for a clinical consultation at one of the five first-level clinical centers in southern Italy from January 2012 to February 2020 were enrolled. All subjects included in the study were screened for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) and anti-HIV; the HBsAg-positive were screened also for anti-delta. Of the 2923 subjects enrolled, 257 (8%) were HBsAg-positive alone (Control group B), 85 (2.9%) only anti-HCV-positive (Control group C), 16 (0.5%) HBsAg/anti-HCV-positive (Case group BC), and 8 (0.2%) HBsAg/anti-HDV-positive (Case group BD). Moreover, 57 (1.9%) subjects were anti-HIV-positive. HBV-DNA positivity was found less frequently in the 16 subjects in Case group BC (43%) and in the 8 in Case group BD (12.5%) than in the 257 in Control group B (76%; p = 0.03 and 0.0000, respectively). Similarly, HCV-RNA positivity was more frequent in Case group BC than in Control group C (75% vs. 44.7% p = 0.02). The subjects in Group BC had a lower prevalence of asymptomatic liver disease (12.5%) than Control group B (62.2%, p = 0.0001) and Control group C (62.3%, p = 0.0002). Conversely, liver cirrhosis was more frequently identified in Case group BC (25%) than in Control groups B and C (3.11% and 2.35%, p = 0.0000 and 0.0004, respectively). The present study contributes to the characterization of hepatitis virus co-infections in the immigrant population.

Hepatitis D virus infection in a large cohort of immigrants in southern Italy: a multicenter, prospective study.

BACKGROUND: Since few data are available in the literature on the prevalence of anti-Delta-positive subjects in immigrant populations, the aim of the present study was to evaluate the demographic and virological characteristics of HDV infection in a large cohort of immigrants living in southern Italy. METHODS: Between January 2012 and February 2020 all immigrants attending one of the 5 first- level centers were enrolled and screened for HBsAg, the HBsAg-positive for anti-Delta and if positive, for HDV-RNA and HDV genotype. RESULTS: Of the 3521 immigrants observed in the study period, 3417 (97.0%) agreed to be screened; they were mainly males (61%), with a median age of 27 years (IQR 8-74) and came prevalently (58%) from sub-Saharan Africa. Of the 3417 patients enrolled, 319 (9%) subjects were HBsAg-positive, and of those, 8 (2.5%) were anti-Delta-positive. No difference in the demographic and epidemiological characteristics was observed between the anti-Delta-negative vs -positive. Of the 8 anti-Delta-positive subjects, only one was HDV-RNA-positive (viral load: 7050 IU/mL), genotype 1, with clinical signs of cirrhosis. CONCLUSIONS: the present study showed a prevalence of HDV of 2.5% in a large cohort of asymptomatic immigrants, suggesting the need for screening campaigns for viral infections including delta hepatitis in this population.