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Aspergillus osteomyelitis is a rare infection. We reviewed 310 individual cases reported in the literature from 1936 to 2013. The median age of patients was 43 years (range, 0–86 years), and 59% were males. Comorbidities associated with this infection included chronic granulomatous disease (19%), haematological malignancies (11%), transplantation (11%), diabetes (6%), pulmonary disease (4%), steroid therapy (4%), and human immunodeficiency virus infection (4%). Sites of infection included the spine (49%), base of the skull, paranasal sinuses and jaw (18%), ribs (9%), long bones (9%), sternum (5%), and chest wall (4%). The most common infecting species were Aspergillus fumigatus (55%), Aspergillus flavus (12%), and Aspergillus nidulans (7%). Sixty-two percent of the individual cases were treated with a combination of an antifungal regimen and surgery. Amphotericin B was the antifungal drug most commonly used, followed by itraconazole and voriconazole. Several combination or sequential therapies were also used experimentally. The overall crude mortality rate was 25%.

We investigated the efficacy of tigecycline and FS8, alone or combined, in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2 x 107 colony-forming units of Staphylococcus aureus, strain Smith diffuse. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis, and three contaminated groups that received: (i) intraperitoneal tigecycline, (ii) FS8-soaked graft, and (iii) tigecycline plus FS8-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro binding-study was performed to quantify the how much FS8 was coated to the surface of the prosthesis. Tigecycline, combined with FS8, against the adherent bacteria showed MICs (2.00 mg/L) and MBCs (4.00 mg/L) four-fold lower with respect to tigecycline alone in in vitro studies. The rat groups treated with tigecycline showed the lowest bacterial numbers (4.4 x 104 ± 1.2 x 104 CFU/mL). The FS8-treated group showed a good activity and significant differences compared to control group with bacterial numbers of 6.8 x 104 ± 2.0 x 104 CFU/mL. A stronger inhibition of bacterial growth was observed in rats treated with a combined FS8 and tigecycline therapy than in those that were singly treated with bacterial numbers of 101 CFU/mL graft. In conclusion, the ability to affect biofilm formation as well, its property to be an antibiotic enhancer suggests FS8 as alternative or additional agent to use in conjunction with conventional antimicrobial for prevention of staphylococcal biofilm related infection.

Chronic hepatitis C virus (HCV) infection has become a leading cause of non-acquired immunodeficiency syndrome (AIDS)-related morbidity and mortality for human immunodeficiency virus (HIV)-infected persons in the highly active antiretroviral therapy (HAART) era. Despite injection drug use (IDU) remaining the main route of HCV infection, recent reports indicate outbreaks of acute HCV infection among HIV-infected men who have sex with men (MSM) and sexually transmitted infections in the absence of IDU.We conducted a retrospective observational study of behavioural and demographic factors of patients with and without incident HCV infection among HIV-infected individuals followed at the AIDS Clinic of the Infectious Disease Department of the University of Ancona from 1989 to 2011.Overall, 440 patients were considered; a total of 145 patients had initial positive HCV antibody test results (HCV+); a total of 295 patients had initial negative HCV antibody test results (HCV-). In the latter population, 14 seroconverted to HCV antibody (neoHCV), with an overall incidence of 0.59 per 100 person-years. While IDU was the principal risk factor of HCV+, the main route of transmission of incident HCV infection was sexual transmission. The HCV- group was significantly older than the other two groups and showed a significantly lower CD4 count at HIV diagnosis than neoHCV. Being Italian and having a low level of education were significantly more represented in HCV+. Younger age at HIV infection, IDU and additional risk factors other than sexual transmission significantly affected the probability of being HCV+. The cumulative probability of developing HCV infection in the HCV- group was calculated to be 6% at 15 years.The epidemiology of the newly acquired HCV in HIV+ persons is changing. Therefore, a frequent and constant counselling about HCV infection is desirable and a periodical screening test is mandatory.

Background: Due to the high efficacy of combination antiretroviral therapy (cART), the number of patients living with HIV is increasing. Chronic HCV infection has become a leading cause of non-AIDS related morbidity and mortality in patients with HIV infection. Objectives: The aim of this cross-sectional study was to identify factors associated with liver fibrosis (LF) in patients with HIV monoinfection and HIV-HCV coinfection. Patients and Methods: We analyzed LF by transient elastometry ((TE), Fibroscan) in three groups of patients (HIV, HIV-HCV and HCV) followed at the Infectious Diseases Department of University of Ancona, Italy, between October 2009 and November 2012. Results: In total, 354 adults including 98 HIV, 70 HIV-HCV and 186 HCV patients were studied. HIV-HCV patients had a longer duration of HIV (P < 0.006) and HCV (P < 0.001) infections. Additionally, they were receiving cART therapy for a longer period (P < 0.001); they had higher prevalence of lipodystrophy (P < 0.001) and higher HCV load (P = 0.004). LF was significantly more pronounced in HCV and HIV-HCV compared to HIV patients (P < 0.001). A total of 13.3%, 39.2% and 51.4% of HIV, HCV and HIV-HCV, respectively, showed a LF ≥ F2. Additionally, a severe LF (F = 4) was significantly more frequent among HIV-HCV compared to other groups. A longer exposure to didanosine, stavudine, lopinavir/ritonavir and fosamprenavir resulted in increased LF by univariate analysis (P ranging from < 0.001 to 0.007). By logistic regression analysis, the only variables significantly associated with increased LF were HCV coinfection, older age, and high AST values (P ranging from < 0.001 to 0.036). Conclusions: HCV coinfection, older age and AST were associated with LF in patients with HIV infection.

Objectives: The aim of the present study was to evaluate the effects of amphotericin B (AMB) on clinical isolates of Aspergillus flavus. Methods: MICs of both standard AMB and liposomal AMB (L-AMB) were determined using a broth dilution method for seven isolates ofA.flavus. AMB MICs were also determined using the Etest. The activity of the polyene was then investigated in a murine model of systemic aspergillosis in which animals were infected intravenously, treated intravenously with several doses of the polyene (1 –10 mg/kg/day) and observed for survival. Results: Broth dilution AMB, broth dilution L-AMB and Etest AMB MICs ranged from 0.5 to 2.0 mg/L, 0.06 to .16 mg/L and 1.0 to .32 mg/L, respectively. There were two isolates for which all doses were effective at prolonging the survival. Their AMB MICs were ≤1.0 mg/L, regardless of the method/drug formulation utilized for testing. There were four isolates for which no regimen was effective. Their broth dilution AMB, broth dilution L-AMB and Etest AMB MICs ranged from 1.0 to 2.0 mg/L, 0.06 to .16 mg/L and 2.0 to .32 mg/L, respectively. There was one isolate for which only L-AMB given at 10 mg/kg/day was effective; broth dilution MICs of AMB and L-AMB were 0.5 mg/L, while the Etest MIC of AMB was 2.0 mg/L. Conclusions: Our data indicate that not all isolates of A. flavus should be considered resistant to AMB. The Etest represented the in vitro method that best correlated with the experimental infection. Finally, a clinical isolate showing an MIC ≥2.0 mg/L may be reasonably considered resistantinvivo to any dose/formulation of the polyene.

The occurrence of resistance or side effects in patients receiving antifungal agents leads to failure in the treatment of mycosis. The aim of this experimental study was to investigate the in vitro effects of IB-367 alone and in combination with three standard antifungal drugs, fluconazole (FLU), itraconazole (ITRA) and terbinafine (TERB), against 20 clinical isolates of dermatophytes belonging to three species. Minimum inhibitory concentrations (MICs), minimal fungicidal concentrations (MFCs), synergy test, time-kill curves, fungal biomass (FB) and hyphal damage using 2,3-bis-(2-methoxy-4-nitro-5-sulfenylamino carbonil)-2H-tetrazolium hydroxide assay (XTT) were performed to study the efficacy of IB-367. In this study, we observed that TERB and ITRA had MICs lower values for all the strains compared to IB-367 and FLU. Synergy was found in 35%, 30% and 25% of IB-367/FLU, IB-367/ITRA and IB-367/TERB interactions respectively. IB-367 exerted a fungicidal activity against Trichophyton mentagrophytes, T. rubrum and Microsporum canis at concentrations starting from 1x MIC. At a concentration of 5x MIC, IB-367 showed the highest rates of hyphae damage for M. canis 53% and T. mentagrophytes 50%; against the same isolates it caused a reduction of 1 log of the total viable count cell hyphae damage. We propose IB-367 as a promising candidate for the future design of antifungal drugs.

E. Gabrielli, A. W. Fothergill, L. Brescini, D. A. Sutton, E. Marchionni, E. Orsetti , S. Staffolani, P. Castelli , R. Gesuita and F. Barchiesi 1) Clinica Malattie Infettive, Universit a Politecnica delle Marche, Ancona, 2) Fungus Testing Laboratory, University of Texas Health Science Center, San Antonio, Texas and 3) Centro di Epidemiologia, Biostatistica e Informatica Medica, Universit a Politecnica delle Marche, Ancona, Italy

Background Infections remain a leading cause of morbidity and mortality among liver transplant (LT) recipients. The aim of our study was to define the factors associated with outcome of early bacterial and fungal infections in a cohort of patients who underwent LT at the University Hospital of Ancona over a nine year period. Methods All consecutive patients who underwent LT in our center were considered. An early infection was defined as occurring in the first month post-transplantation. Results Among 330 patients who underwent LT from August 2005 to October 2014, 88 (27 %) had at least one infection documented within 30 days after transplantation. In 54 cases only one site was involved, in 34 cases ≥2 sites. There were 43 (30 %) pneumonia, 40 (27 %) surgical site infections, 31 (22 %) blood stream infections, and 30 (21 %) urinary tract infections. Gram-negative bacteria accounted for 64 % of the culture-positive cases, followed by Gram-positive bacteria (30 %) and fungi (6 %). A high proportion of drug-resistant strains was found within either Gram-negative (79 %) or Gram-positive (81 %) bacteria. There were 27 out 88 patients (31 %) who died within 180 days from the transplant. Factors independently associated with a higher risk of mortality were: renal replacement therapy (HR 11.797 [CI95 % 3.082–45.152], p