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This study aimed to compare the clinical progression of COVID-19 in high-risk outpatients treated with the monoclonal antibodies (mAb) bamlanivimab, bamlanivimab-etesevimab and casirivimab-imdevimab. This is an observational, multi-centre, prospective study conducted from 18 March to 15 July 2021 in eight Italian tertiary-care hospitals including mild-to-moderate COVID-19 outpatients receiving bamlanivimab (700 mg), bamlanivimab-etesevimab (700-1400 mg) or casirivimab-imdevimab (1200-1200 mg). All patients were at high risk of COVID-19 progression according to Italian Medicines Agency definitions. In a patient subgroup, SARS-CoV-2 variant and anti-SARS-CoV-2 serology were analysed at baseline. Factors associated with 28-day all-cause hospitalisation were identified using multivariable multilevel logistic regression (MMLR) and summarised with adjusted odds ratio (aOR) and 95% confidence interval (CI). A total of 635 outpatients received mAb: 161 (25.4%) bamlanivimab, 396 (62.4%) bamlanivimab-etesevimab and 78 (12.2%) casirivimab-imdevimab. Ninety-five (15%) patients received full or partial SARS-CoV-2 vaccination. The B.1.1.7 (Alpha) variant was detected in 99% of patients. Baseline serology showed no significant differences among the three mAb regimen groups. Twenty-eight-day all-cause hospitalisation was 11.3%, with a significantly higher proportion (p 0.001) in the bamlanivimab group (18.6%), compared to the bamlanivimab-etesevimab (10.1%) and casirivimab-imdevimab (2.6%) groups. On MMLR, aORs for 28-day all-cause hospitalisation were significantly lower in patients receiving bamlanivimab-etesevimab (aOR 0.51, 95% CI 0.30-0.88 p 0.015) and casirivimab-imdevimab (aOR 0.14, 95% CI 0.03-0.61, p 0.009) compared to those receiving bamlanivimab. No patients with a history of vaccination were hospitalised. The study suggests differences in clinical outcomes among the first available mAb regimens for treating high-risk COVID-19 outpatients. Randomised trials are needed to compare efficacy of mAb combination regimens in high-risk populations and according to circulating variants., (© 2022. The Author(s).)

The purpose of this investigation was to assess the balance between the personal and professional lives of trainees and young European specialists in clinical microbiology (CM) and infectious diseases (ID), and determine differences according to gender, country of training, workplace and specialty. The Steering Committee of the Trainee Association of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) devised a questionnaire survey consisting, beyond the demographic questions, of nine yes/no questions, 11 Likert scale self-evaluations and one open-response item on parenthood, working conditions, quality of life, alcohol consumption and burnout. This anonymous survey in English was held between April and July 2015 among European CM/ID trainees and young specialists (<3 years after training completion). Responses from 416 participants with a mean age of 32 years [standard deviation (SD) 5 years] were analysed. Females and physicians from Northern/Western Europe (NWE) benefit more from paternity/maternity leaves even during training than their counterparts. Among all respondents, only half of breastfeeding mothers enjoyed the benefit of working hours flexibility. Only two-thirds of respondents found their working environment stimulating. In comparison to colleagues from other parts of Europe, trainees and young specialists from Southern/Eastern Europe (SEE) had less frequent regular meetings with mentors/supervisors and head of departments where trainees' issues are discussed. Also, physicians from SEE were more frequently victims of workplace mobbing/bullying in comparison to those from other regions. Finally, multivariate analysis showed that female gender, SEE region and ID specialty were associated with burnout feelings. Female gender and country of work from SEE largely determine satisfactory working conditions, the possibility of parenthood leaves, amount of leisure time, mobbing experiences and burnout feelings among European CM/ID trainees and young specialists.

The purpose of this investigation was to perform a survey among European clinical microbiology (CM) and infectious disease (ID) trainees on training satisfaction, training tools, and competency assessment. An online, anonymous survey in the English language was carried out between April and July 2015. There were 25 questions: seven in a 5-point Likert scale (1: worst scenario, 5: best scenario) and the remainder as closed multiple-choice questions in five areas (satisfaction, adequacy, system, mentorship, and evaluation of training). Included were 419 respondents (215 CM, 159 ID, and 45 combined CM/ID) from 31 European countries [mean age (standard deviation) 32.4 (5.3) years, 65.9 % women]. Regarding satisfaction on the training scheme, CM and ID scored 3.6 (0.9) and 3.2 (1.0), respectively. These scores varied between countries, ranging from 2.5 (1.0) for Italian ID to 4.3 (0.8) for Danish CM trainees. The majority of respondents considered training in management and health economics inadequate and e-learning and continuing medical education programs insufficient. Many trainees (65.3 % of CM and 62.9 % of ID) would like to have more opportunities to spend a part of their training abroad and expected their mentor to be more involved in helping with future career plans (63.5 % of CM and 53.4 % of ID) and practical skills (53.0 % of CM and 61.2 % of ID). Two-thirds of the respondents across the specialties agreed that a European exam should be developed, but half of them thought it should not be made mandatory. This survey shows high heterogeneity in training conditions in European countries, identifies perceived gaps in training, and suggests areas for improvements., Competing Interests: Compliance with ethical standards Funding The study was supported by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID).

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare complication of bisphosphonate treatment characterized by the development of exposed, necrotic bone in the jaw with inflammatory signs. The pathogenesis of BRONJ is not yet fully understood. This review analyzes the evidence supporting the hypothesis that BRONJ may be considered as a bisphosphonate-induced Actinomyces infection of the jaw according to the modified Koch's postulates. The main arguments relies on the following factors: (1) the high prevalence of isolation of Actinomyces from bone BRONJ lesions (73.2 % in retrospective series); (2) the similar pathological appearance of BRONJ and Actinomyces osteomyelitis in most studies, although BRONJ lesions without inflammation have been reported; (3) the high incidence of events that disrupt the normal mucosal barrier as a necessary trigger to develop BRONJ in bisphosphonate-exposed patients; (4) the predilection of bisphosphonate-induced osteonecrosis for the bones of the jaws; and (5) the favorable response of BRONJ on treatment that is active on Actinomyces. If BRONJ confirms to be a bisphosphonate-induced Actinomyces osteomyelitis of the jaw, this has major consequences for the prevention and treatment of this condition.

In order to elucidate the factors related to the development of cidofovir-associated uveitis in AIDS patients receiving highly active antiretroviral therapy, the characteristics of 17 AIDS patients with Cytomegalovirus retinitis ( n=10) or progressive multifocal leukoencephalopathy ( n=7) treated with intravenous cidofovir were evaluated. Six cases of cidofovir-associated uveitis occurred among the patients with retinitis. No cases were detected among the patients with progressive multifocal leukoencephalopathy. Stepwise linear regression analysis revealed a significantly higher HIV-viremia level ( P=0.01) and a significantly lower CD4+ cell count ( P=0.009) among cases at the time of uveitis onset in comparison with patients who did not develop uveitis. Thus, cidofovir-associated uveitis seems to occur more frequently in AIDS patients with retinitis in whom highly active antiretroviral therapy fails to restore immunity.

The aim of the study presented here was to determine the incidence, risk factors and prognostic indicators of Mycobacterium avium complex (MAC) infection in HIV-infected subjects prior to and after the introduction of highly active antiretroviral therapy (HAART). In the HAART era, the incidence of MAC infection decreased significantly from 3.7 to 0.9 per 100 person-years. Using logistic regression analysis, a high acute physiology and chronic health evaluation (APACHE) III score, a low number of CD4+ cells/ mm3 and a high level of HIV viremia were found to be independent predictors of the risk to develop MAC disease; however, a high APACHE III score was the only prognostic indicator associated with an unfavourable outcome of a disseminated MAC infection. These results indicate that MAC infections, although considerably less frequent in the HAART era, are still responsible for cases of severe disease.

The epidemiological features of 37 episodes of candidemia in HIV-infected subjects were analysed in a retrospective matched case-control study conducted over an 8-year period (1990-1997). Univariate analysis identified eight risk factors that were significantly associated with candidemia (P<0.05): i) use of central venous catheters; ii) administration of total parenteral nutrition; iii) previous antifungal therapy; iv) previous therapy with glycopeptides; v) presence of oral/ esophageal candidiasis; vi) concomitant bacterial infections; vii) neutropenia; and viii) concomitant AIDS dementia complex. Stepwise logistic regression analysis revealed that the only independent risk factor for developing candidemia was the use of central venous catheters (P = 0.0001). Candida albicans was the most frequently isolated pathogen, accounting for 18 (48%) episodes of candidemia, followed by Candida tropicalis (19%) and Candida glabrata (11%). The crude mortality rate was 62%. On univariate analysis concomitant opportunistic infections, presence of non-Candida albicans species of Candida and neutropenia were shown to be predictive of death. Multivariate analysis revealed that the presence of non-Candida albicans strains of Candida was the only significant factor associated with a worse prognosis (P = 0.001). In conclusion, candidemia appears to be more common in patients with advanced HIV disease. Of the factors which influenced the onset of candidemia, use of central venous catheters seemed to be the most important one.

Five hundred two central venous catheters inserted in 366 patients were evaluated prospectively over a one-year period to determine the frequency and risk factors associated with catheter-related sepsis. For study purposes, in cases in which catheter infection was suspected but the initial blood cultures were negative, the catheters were replaced by guidewire technique; otherwise, the catheters were routinely changed after 21 days by guidewire technique. A catheter-related infection was suspected in 190 cases (190/502, 38%). A diagnosis of catheter-related sepsis was established in 50 patients, which represents 10% of the total number of lines (502). Over a total of 6428 days of catheter use, the infection rate was 0.8 cases of sepsis per 100 catheter-days. Staphylococcus epidermidis, Staphylococcus aureus, and Candida spp. were the most frequently isolated aetiological agents of sepsis. On univariate analysis, six variables affecting the rate of catheter-related sepsis were identified: neutropenia for more than eight days (p < 0.001); AIDS (p < 0.001); haematological malignancy (p < 0.001); administration of total parenteral nutrition (p = 0.001); duration of site use (p = 0.04); and high APACHE II score (p = 0.04). The logistic regression analysis revealed that AIDS and haematological malignancies were independent risk factors of catheter-related sepsis. Catheter replacement over a guidewire was no more likely to be associated with sepsis than was percutaneous catheter insertion. In conclusion, although the incidence of established catheter infection is much lower than the incidence of suspected infection, in most cases of suspected infection it is wise to change the catheter with the guidewire technique and wait for culture of the tip, rather than to remove the catheter immediately. Such a policy may help reduce the number of unnecessary catheter removals.