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[Purpose] The purpose of this study was the clinical and therapeutic assessment of lower-limb osteosynthesis-associated infection (OAI) by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), which have been poorly studied to date., [Methods] A prospective multicentre observational study was conducted on behalf of ESGIAI (the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group on Implant-Associated Infections). Factors associated with remission of the infection were evaluated by multivariate and Cox regression analysis for a 24-month follow-up period., [Results] Patients ( n=57 ) had a history of trauma (87.7 %), tumour resection (7 %) and other bone lesions (5.3 %). Pathogens included Escherichia coli ( n=16 ), Pseudomonas aeruginosa ( n=14 ; XDR 50 %), Klebsiella spp. ( n=7 ), Enterobacter spp. ( n=9 ), Acinetobacter spp. ( n=5 ), Proteus mirabilis ( n=3 ), Serratia marcescens ( n=2 ) and Stenotrophomonas maltophilia ( n=1 ). The prevalence of ESBL (extended-spectrum β -lactamase), fluoroquinolone and carbapenem resistance were 71.9 %, 59.6 % and 17.5 % respectively. Most patients ( n=37 ; 64.9 %) were treated with a combination including carbapenems ( n=32 ) and colistin ( n=11 ) for a mean of 63.3 d. Implant retention with debridement occurred in early OAI (66.7 %), whereas the infected device was removed in late OAI (70.4 %) ( p=0.008 ). OAI remission was achieved in 29 cases (50.9 %). The type of surgery, antimicrobial resistance and duration of treatment did not significantly influence the outcome. Independent predictors of the failure to eradicate OAI were age >60 years (hazard ratio, HR, of 3.875; 95 % confidence interval, CI95 %, of 1.540-9.752; p=0.004 ) and multiple surgeries for OAI (HR of 2.822; CI95 % of 1.144-6.963; p=0.024 )., [Conclusions] Only half of the MDR/XDR GNB OAI cases treated by antimicrobials and surgery had a successful outcome. Advanced age and multiple surgeries hampered the eradication of OAI. Optimal therapeutic options remain a challenge.

Interferon-γ releasing assays (IGRAs) are currently widely employed in the initial work up of Mycobacterium tuberculosis infection, as well as in suspected tuberculosis (TB). These assays are commonly utilized over the Tuberculin Skin Test (TST) in high resource and low TB burden settings, despite the unclear benefits shown in such contexts. The debate on the use of TST and IGRAs is of current interest also in Italy due to the increasing presence of immigrants from countries with a high incidence of TB and the rising attention of health care institutions to economic costs. The aim of this study was to compare QuantiFERON-TB (QFT) and TST results in active TB. We evaluated QFT results and TST reactions from 245 consecutive patients having both tests, registered among 411 patients admitted for TB at the Infectious Disease Clinic, Department of Medicine of the University of Perugia (Italy). We compared the rates of positive QFT and TST tests and noted no statistically significant differences overall or in relation to age, gender, HIV status and TB localization. Among foreign-born patients with confirmed TB, we observed a lower rate of positive TST results. The results of our study indicated that both QFT and TST can be used in the work up of TB having special attention when evaluating foreign-born patients.

Objective: To investigate predisposing factors and outcomes of non-HACEK Gram-negative bacilli (GNB) infective endocarditis (IE) in a multicenter, contemporary cohort.Patients and Methods:Patients with IE due to GNB prospectively observed in 26 Italian centers from 2004 to 2011 were analyzed. Using a case-control design, each case was compared to three controls with IE by other etiologies matched for age and sex. Logistic regression was performed to identify risk factors for GNB IE. Factors associated with early and late mortality were assessed by Cox regression analysis.Results:The study group comprised 58 patients with GNB IE.Escherichia coliwas the most common pathogen followed byPseudomonas aeruginosaandKlebsiella pneumoniaeGenitourinary tract as source of infection (OR 13.59, 95% CI 4.63-39.93, p

Factors influencing treatment outcome of patients with Gram-negative bacterial (GNB) multidrug-resistant (MDR) and extensively drug-resistant (XDR) prosthetic joint infection (PJIs) were analysed. Data were collected (2000–2015) by 18 centres. Treatment success was analysed by surgery type for PJI, resistance (MDR/XDR) and antimicrobials (colistin/non-colistin) using logistic regression and survival analyses. A total of 131 patients (mean age 73.0 years, 35.9% male, 58.8% with co-morbidities) with MDR (n = 108) or XDR (n = 23) GNB PJI were assessed. The most common pathogens were Escherichia coli (33.6%), Pseudomonas aeruginosa (25.2%), Klebsiella pneumoniae (21.4%) and Enterobacter cloacae (17.6%). Pseudomonas aeruginosa predominated in XDR cases. Isolates were carbapenem-resistant (n = 12), fluoroquinolone-resistant (n = 63) and ESBL-producers (n = 94). Treatment outcome was worse in XDR versus MDR cases (P = 0.018). Success rates did not differ for colistin versus non-colistin in XDR cases (P = 0.657), but colistin was less successful in MDR cases (P = 0.018). Debridement, antibiotics and implant retention (DAIR) (n = 67) was associated with higher failure rates versus non-DAIR (n = 64) (OR = 3.57, 95% CI 1.68–7.58; P < 0.001). Superiority of non-DAIR was confirmed by Kaplan–Meir analysis (HR = 0.36, 95% CI 0.20–0.67) and remained unchangeable by time of infection (early/late), antimicrobial resistance (MDR/XDR) and antimicrobials (colistin/non-colistin) (Breslow–Day, P = 0.737). DAIR is associated with higher failure rates even in early MDR/XDR GNB PJIs versus implant removal. Colistin should be preserved for XDR cases as it is detrimental in MDR infections., Statistical analysis of the study was performed with the financial support of the Hellenic Institute for the Study of Sepsis.

Prosthetic joint infections (PJI) caused by nontuberculous mycobacteria are very rare, and results of treatment can be unpredictable. A 72-year-old female underwent hip replacement after an accidental fall in a local hospital in Santo Domingo. The postoperative period was uneventful except for a traumatic wound near the surgical scar. PJI caused by Mycobacterium abscessus subsp. abscessus was diagnosed 6 months later. A two-stage reimplantation was performed after a 3-month period of aetiology-directed therapy, including amikacin, imipenem, and clarithromycin. M. abscessus isolate was reported to be resistant to clarithromycin when incubation was protracted for 14 days and to harbour the gene erm(41). The patient manifested major side effects to tigecycline. At reimplant, microbiologic investigations resulted negative. Overall, medical treatment was continued for a 7-month period. When discontinued and at 6-month follow-up, the patient was clinically well, inflammatory markers were normal, and the radiography showed well-positioned prosthesis. Mycobacterium abscessus subsp. abscessus is a very rare cause of PJI, yet it must be included in the differential diagnosis, especially when routine bacteria cultures are reported being negative. Further investigations are needed to determine any correlations between clinical results and in vitro susceptibility tests, as well as the clinical implications of M. abscessus subsp. abscessus harbouring the functional gene erm(41). Moreover, investigations are needed for determine optimal timings of surgery and lengths of medical therapy to improve patient outcome.

Histoplasma capsulatum is a dimorphic fungus, endemic in the Americas, Africa (var. duboisii), India, and Southeast Asia. H. capsulatum infection is rarely diagnosed in Italy, while in Latin America, progressive disseminated histoplasmosis (PDH) is one of the most frequent AIDS-defining illnesses and causes of AIDS-related deaths. We report a case of PDH and new HIV infection diagnosis in a Cuban patient, who has been living in Italy for the past 10 years. Bone marrow aspirate and peripheral blood smear microscopy suggested H. capsulatum infection. The diagnosis was confirmed with the culture method identifying its thermal dimorphism. Liposomal amphotericin B was administered alone for 10 days and then for another 2 days, accompanied with voriconazole; the former was stopped for probable side effects (persistent fever and worsening thrombocytopenia), and voriconazole was continued to complete 4 weeks. PDH maintenance treatment consisted of itraconazole for one year. Antiretroviral therapy (ART) was started on the third week of antifungal treatment. At the 3-year follow-up, the patient is adherent on ART, the virus was suppressed, and she has an optimal immune recovery. This case highlights the need to suspect histoplasmosis in the differential diagnosis of opportunistic infections in immunocompromised persons, native to or who have traveled to endemic countries.

Borrelia crocidurae is endemic in West Africa, where it represents the leading cause of tick-borne relapsing fever (TBRF). TBRF typically presents with high fever and systemic symptoms, followed by recurrent episodes. Neurological complications may occur during febrile relapses. B. crocidurae is considered the most neurotropic agent of TBRF and is associated to severe neurological manifestations i.e. meningitis and encephalitis. To date, European cases of B. crocidurae infection have been reported in travelers returning from endemic areas. We report the first autochthonous case in Europe of B. crocidurae infection, presenting as meningitis with cranial polyneuritis and cavernous sinus thrombosis that were not preceded by classic febrile recurrences.

Background TRAIL, TNF-related apoptosis-induced ligand, is a novel biomarker of viral infection. In healthy individuals, circulating levels are typically ~ 80 pg/mL, but in the setting of viral infection, levels increase within hours. Recent studies have found decreased TRAIL levels to be correlated with disease severity in conditions such as cardiovascular disease and ischemic stroke. However, nothing is known about its role as a severity marker for children with viral infections. Here we examined, for the first time, whether TRAIL levels are associated with viral disease severity in children. Methods “AutoPilot-Dx” (NCT03052088) is an EU funded, multinational, prospective study designed to validate diagnostic performance of a TRAIL, IP-10, and CRP protein signature for differentiating between bacterial and viral infections. We analyzed the first 657 eligible children. Viral etiology was assigned by majority adjudication of three experts based on comprehensive investigation including follow-up questionnaires and multiplex respiratory PCR panel (Allplex™). Children hospitalized for > 5 days, had lowest saturation of < 96% and appeared ill on physical examination were defined as having severe viral infection. Serum TRAIL levels were measured using ELISA (ImmunoXpert™). Results Of the 657 children adjudicated, 465 were classified as viral. Of them, 317 and 57 were defined as having non-severe and severe viral disease, respectively (Figure 1). TRAIL levels were markedly increased in all viral patients (mean ± SD [pg/mL]: 151 ± 111). Patients with severe viral infection exhibited significantly lower TRAIL levels when compared with non-severe infection (non-severe 158 ± 114; severe 107 ± 60; P = 0.001), implying that viral-induced TRAIL levels may be counterbalanced by the severity state. Age and time from fever onset were not found to be confounders. Notably, common bacterial markers such as CRP (non-severe 20 ± 26; severe 17 ± 16; P = 0.549), WBC (non-severe 11 ± 5; severe 12 ± 5; P = 0.074) and ANC (non-severe 7 ± 4; severe 7 ± 3; P = 0.410) exhibited no significant difference between the groups. Conclusion Serum TRAIL levels were significantly associated with viral disease severity, suggesting its potential as a prognostic marker for viral-infected children. Disclosures All authors: No reported disclosures.

In 1998 a network of 20 regional tuberculosis (TB) laboratories (the Italian Multicentre Study on Resistance to Antituberculosis drugs (SMIRA) network) was established in Italy to implement proficiency testing and to monitor the prevalence of drug resistance nationwide. The network managed 30% of all TB cases reported in Italy each year. The aim of the present report is to describe: 1) the accuracy of drug-susceptibility testing in the network; 2) the prevalence of drug resistance for the period 1998-2000. Data were collected from the network laboratories. Sensitivity to streptomycin and ethambutol increased from the first survey (1998-1999) to the second survey (2000) from 87.7 to 91.9%. Specificity, predictive values for resistance and susceptibility, efficiency and reproducibility were consistent in both surveys. In previously untreated cases, the prevalence of multidrug-resistance was the same in both surveys (1.2%), while a slight decrease from the first to the second survey was observed for monoresistance to rifampicin (from 0.8 to 0.4%) and isoniazid (from 2.9 to 2%). The significant association found between isoniazid resistance and immigration is a useful indicator for both clinicians managing individual tuberculosis cases and public health services planning control strategies.

The aim of this study was to evaluate the epidemiological and clinical characteristics of 232 cases of infective endocarditis (IE), admitted to the Clinica delle Malattie Infettive of Perugia Italy from 1973 to 2012. The analysis was retrospective until 2004. After this year, all the consecutive IE cases were included by utilizing the same prospective observational protocol of the Italian Study on Endocarditis (SEI). Out of 232 EI cases, 200 (86.2 %) were definite. Over the 40-year period, a statistically significant increase was observed in the patients' age, the rate of IE admissions and prosthetic device IEs. The rate of healthcare-associated IEs also increased in the last 10 years (p=NS). Diabetes mellitus was the most frequent comorbidity. There were no variations in the rate of S. aureus and streptococcal IEs. Central nervous system complications and surgery were reported in 19.4 percent and 29.3 percent of the cases, respectively. The in-hospital mortality was 18.9 percent. In conclusion, the epidemiological and clinical trends of this study are in agreement with the literature. The difference in S. aureus endocarditis, neurological complications and surgery rates may be due to the fact that this was a single centre and, for its first part, a retrospective study. A shared, multidisciplinary protocol may be useful to improve the outcome of patients with IE and its epidemiology.

In order to describe the trend of syphilis at the Infectious Diseases Clinic of Perugia University, Italy, over a six-year period (2005-2010), 138 patients were identified and monitored. Syphilis diagnosis was as follows: latent 60%, secondary 21%, neurosyphilis 10%, primary 9%. The study population comprised 83% males, 59% Italians and 45% men who have sex with men (MSMs). Heterosexual females represented 28.5% cases among immigrants and 8.5% cases among Italians, while men with unknown sexual contacts were 28% and 14% respectively (p=0.0059). HIV co-infection was detected in 70% of patients, with a predominance of males (94%) and Italians (62%). Among HIV-positive patients, 63% were pre-existing HIV-infected: of these, 26% had primary or secondary syphilis. During the study period, the number of regional syphilis notifications at the Italian Health Department was lower with respect to the observed cases at the Infectious Diseases Clinic of Perugia (69 versus 138). Globally, the trend of syphilis infection remained stable over the six-year period. However, efforts to improve prevention and screening programs are required for persons at risk of both syphilis and HIV infection, as well as measures to strengthen syphilis notification procedures.

Trends in tuberculosis (TB) admissions over 40 years at the Infectious Diseases Clinic of Perugia University Hospital, Perugia, Italy, show that in the last decade non-Italian TB case admissions outweighed those of Italians, with a large number of cases from Eastern Europe (25.2%) and Africa (23.4%). Non-Italians tended to be younger and were generally new pulmonary TB cases, and drug resistance was also more common. Overall, the number of multidrug-resistant cases increased. Only one case occurred in a native-born Italian, and five of seven cases had newly diagnosed TB. In low TB incidence settings such as Perugia, Italy, TB prevention and control programmes for the foreign-born need to be reinforced.

Here we report on two consecutive cases of tuberculosis in immunocompetent HIV-negative patients with lingual lesions. In both patients diagnosis was delayed. Disease progressed involving the lungs, lymph nodes and also the brain. Both patients are disease-free at 30 and 22 month follow-up respectively. Isolated Mycobacterium tuberculosis from these patients was multi-susceptible. Tuberculosis lesions of the oral cavity and brain are infrequently diagnosed in immunocompetent subjects from Western countries. Clinicians must take into greater consideration tuberculosis as a possible diagnosis when diagnosing chronic and/or recurrent lingual lesions even in the absence of pulmonary lesions.