Six-month humoral and cellular immune response to the third dose of BNT162b2 anti-SARS-CoV-2 vaccine in patients with solid tumors: a longitudinal cohort study with a focus on the variants of concern.

BACKGROUND: The role and the durability of the immunogenicity of the third dose of vaccine against COVID-19 variants of concern in cancer patients have to be elucidated. PATIENTS AND METHODS: We have prospectively evaluated the immunogenicity of the third dose of the SARS-CoV-2 BNT162b2 messenger RNA vaccine in triggering both humoral and cell-mediated immune response in patients with solid tumors undergoing active treatment 6 months after the booster. Neutralizing antibody (NT Ab) titers and total anti-spike immunoglobulin G concentrations were measured in serum. Heparinized whole blood samples were used for the SARS-CoV-2 interferon-γ release assay (IGRA). RESULTS: Six months after the third dose only two patients (2.4%) showed negative spike-specific immunoglobulin G antibody levels (<33.8 BAU/ml). The median level of SARS-CoV-2 NT Abs decreased and only 39/83 (47%) subjects showed maximum levels of NT Abs. T-cellular positive response was observed in 38/61 (62.3%) patients; the highest median level of response was observed 21 days after the third dose (354 mIU/ml, interquartile range 83.3-846.3 mIU/ml). The lowest median level of NT Ab response was observed against the Omicron variant (1 : 10, interquartile range 1 : 10-1 : 40) with a significant reduced rate of responder subjects with respect to the wild-type strain (77.5% versus 95%; P = 0.0022) and Delta variant (77.5% versus 93.7%; P = 0.0053). During the follow-up period, seven patients (8%) had a confirmed post-vaccination infection, but none of them required hospitalization or oxygen therapy. CONCLUSIONS: Our work highlights a significant humoral and cellular immune response among patients with solid tumors 6 months after the third BNT162b2 vaccine dose, although a reduction in neutralizing activity against Omicron was observed.

Immunogenicity and safety after the third dose of BNT162b2 anti-SARS-CoV-2 vaccine in patients with solid tumors on active treatment: a prospective cohort study.

BACKGROUND: Although a full course of coronavirus disease 2019 (COVID-19) vaccine is effective in cancer patients, the duration of the protection and the efficacy of a booster dose against the new variants remain unknown. We prospectively evaluated the immunogenicity of the third dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BNT162b2 messenger RNA vaccine in cancer patients undergoing active treatment. PATIENTS AND METHODS: Patients with solid cancer, vaccinated with a booster dose during active treatment, were enrolled in this study. Patients were classified into SARS-CoV-2 naïve (without previous COVID-19 infection) and SARS-CoV-2 experienced (with previous COVID-19 infection). Neutralizing antibody (NT Ab) titer and total anti-Spike immunoglobulin G (IgG) concentration were quantified in serum. Heparinized whole blood samples were used for SARS-CoV-2 Interferon Gamma Release Assay (IGRA). The primary endpoint was to assess the increase of IgG antibody level between baseline and 3 weeks after the booster. RESULTS: One hundred and forty-two consecutive patients were recruited. In SARS-CoV-2-naïve subjects, the median level of IgG was 157 BAU/ml [interquartile range (IQR) 62-423 BAU/ml] at T0 and reached a median of 2080 BAU/ml (IQR 2080-2080 BAU/ml) at 3 weeks after booster administration (T1; P < 0.0001). A median 16-fold increase of SARS-CoV-2 NT Ab titer (IQR 4-32) was observed in naïve subjects (from median 20, IQR 10-40, to median 640, IQR 160-640; P < 0.0001). Median interferon-γ level at T1 was significantly higher than that measured at T0 in SARS-CoV-2-naïve subjects (P = 0.0049) but not in SARS-CoV-2-experienced patients. The median level of SARS-CoV-2 NT Abs was 32-fold lower against Omicron compared to the wild-type strain (P = 0.0004) and 12-fold lower compared to the Delta strain (P = 0.0110). CONCLUSIONS: The third dose is able to trigger both the humoral and the cell-mediated immune response in cancer patients on active treatment. Our preliminary data about the neutralization of the SARS-CoV-2 vaccine against variants of concern seem to confirm the lower vaccine activity.

Analysis of the humoral and cellular immune response after a full course of BNT162b2 anti-SARS-CoV-2 vaccine in cancer patients treated with PD-1/PD-L1 inhibitors with or without chemotherapy: an update after 6 months of follow-up.

BACKGROUND: The durability of immunogenicity of SARS-CoV-2 vaccination in cancer patients remains to be elucidated. We prospectively evaluated the immunogenicity of the vaccine in triggering both the humoral and the cell-mediated immune response in cancer patients treated with anti-programmed cell death protein 1/programmed death-ligand 1 with or without chemotherapy 6 months after BNT162b2 vaccine. PATIENTS AND METHODS: In the previous study, 88 patients were enrolled, whereas the analyses below refer to the 60 patients still on immunotherapy at the time of the follow-up. According to previous SARS-CoV-2 exposure, patients were classified as SARS-CoV-2-naive (without previous SARS-CoV-2 exposure) and SARS-CoV-2-experienced (with previous SARS-CoV-2 infection). Neutralizing antibody (NT Ab) titer against the B.1.1 strain and total anti-spike immunoglobulin G concentration were quantified in serum samples. The enzyme-linked immunosorbent spot assay was used for quantification of anti-spike interferon-γ (IFN-γ)-producing cells/106 peripheral blood mononuclear cells. Fifty patients (83.0%) were on immunotherapy alone, whereas 10 patients (7%) were on chemo-immunotherapy. We analyzed separately patients on immunotherapy and patients on chemo-immunotherapy. RESULTS: The median T-cell response at 6 months was significantly lower than that measured at 3 weeks after vaccination [50 interquartile range (IQR) 20-118.8 versus 175 IQR 67.5-371.3 IFN-γ-producing cells/106 peripheral blood mononuclear cells; P < 0.0001]. The median reduction of immunoglobulin G concentration was 88% in SARS-CoV-2-naive subjects and 2.1% in SARS-CoV-2-experienced subjects. SARS-CoV-2 NT Ab titer was maintained in SARS-CoV-2-experienced subjects, whereas a significant decrease was observed in SARS-CoV-2-naive subjects (from median 1 : 160, IQR 1 : 40-1 : 640 to median 1 : 20, IQR 1 : 10-1 : 40; P < 0.0001). A weak correlation was observed between SARS-CoV-2 NT Ab titer and spike-specific IFN-γ-producing cells at both 6 months and 3 weeks after vaccination (r = 0.467; P = 0.0002 and r = 0.428; P = 0.0006, respectively). CONCLUSIONS: Our work highlights a reduction in the immune response in cancer patients, particularly in SARS-CoV-2-naive subjects. Our data support administering a third dose of COVID-19 vaccine to cancer patients treated with programmed cell death protein 1/programmed death-ligand 1 inhibitors.

A snapshot of the immunogenicity, efficacy and safety of a full course of BNT162b2 anti-SARS-CoV-2 vaccine in cancer patients treated with PD-1/PD-L1 inhibitors: a longitudinal cohort study.

BACKGROUND: Very few cancer patients were enrolled in coronavirus disease-2019 vaccine studies. In order to address this gap of knowledge, real-world studies are mandatory. The aim of this study was to assess both humoral and cellular response after a messenger RNA vaccination schedule. PATIENTS AND METHODS: Eighty-eight consecutive cancer patients treated with programmed cell death protein 1/programmed death-ligand 1 inhibitors were enrolled from the beginning of the vaccination campaign for frail patients. Blood samples for humoral and cell-mediated immune response evaluation were obtained before vaccination (T0), before the second administration (T1) and 21 days after the second dose (T2). The primary endpoint was the evaluation of the percentage of participants showing a significant increase in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells, measured by an enzyme-linked immunospot assay, after the second dose of BNT162b2 vaccine. The proportion of patients who reached the primary endpoint is computed together with its exact binomial 95% confidence interval. RESULTS: In SARS-CoV-2-naïve subjects, spike-specific T-cell response was almost undetectable at T0 [median 0.0 interferon-γ (IFN-γ) spot forming units (SFU)/million peripheral blood mononuclear cell (PBMC) interquartile range (IQR) 0-7.5] and significantly increased at T1 and T2 (median 15.0 IFN-γ SFU/million PBMC, 25th-75th 0-40 versus 90 IFN-γ SFU/million PBMC, 25th-75th 32.5-224, respectively) (P < 0.001). Focusing on naïve and experienced SARS-CoV-2 subjects, no differences were reported both in terms of CD4- and CD8-specific T-cell response, suggesting that BNT162b2 is able to elicit both adaptive responses after complete vaccination schedule, regardless of previous SARS-CoV-2 exposure. The level of SARS-CoV-2 neutralizing antibodies was low at T1 in SARS-CoV-2-naïve subjects [median 1 : 5 (IQR 1 : 5-1 : 20)] but reached a significantly higher median of 1 : 80 (25th-75th 1 : 20-1 : 160) at T2 (P < 0.0001). Moreover, no COVID-19 cases were documented throughout the period of study. CONCLUSIONS: Our data have demonstrated that the administration of a full course of BNT162b2 vaccine elicited a sustained immune response against SARS-CoV-2 regardless of the type of cancer and/or the type of immune checkpoint inhibitors.

Estimating COVID-19 recovery time in a cohort of Italian healthcare workers who underwent surveillance swab testing.

OBJECTIVES: The COVID-19 pandemic is putting a huge strain on the provision and continuity of care. The length of sickness absence of the healthcare workers as a result of SARS-CoV-2 infection plays a pivotal role in hospital staff management. Therefore, the aim of this study was to explore the timing of COVID-19 recovery and viral clearance, and its predictive factors, in a large sample of healthcare workers. STUDY DESIGN: This is a retrospective cohort study. METHODS: The analysis was conducted on data collected during the hospital health surveillance programme for healthcare staff at the University Hospital of Verona; healthcare workers were tested for SARS-CoV-2 through RT-PCR with oronasopharyngeal swab samples. The health surveillance programme targeted healthcare workers who either had close contact with SARS-CoV-2-infected patients or were tested as part of the screening-based strategy implemented according to national and regional requirements. Recovery time was estimated from the first positive swab to two consecutive negative swabs, collected 24 h apart, using survival analysis for both right-censored and interval-censored data. Cox proportional hazard was used for multivariate analysis. RESULTS: During the health surveillance programme, 6455 healthcare workers were tested for SARS-CoV-2 and 248 (3.8%, 95% confidence interval [CI]: 3.4-4.3) reported positive results; among those who tested positive, 49% were asymptomatic, with a median age of 39.8 years, which is significantly younger than symptomatic healthcare workers (48.2 years, P < 0.001). Screening tests as part of the health surveillance programme identified 31 (12.5%) of the positive cases. Median recovery time was 24 days (95% CI: 23-26) and 21.5 days (95% CI: 15.5-30.5) in right- and interval-censoring analysis, respectively, with no association with age, sex or presence of symptoms. Overall, 63% of participants required >20 days to test negative on two consecutive swabs. Hospitalised healthcare workers (4.8%) were older and had a significantly longer recovery time compared with non-hospitalised healthcare workers in both analyses (33.5 vs 24 days, P = 0.005). CONCLUSIONS: Recovery from COVID-19 and viral clearance may take a long time, especially in individuals who are hospitalised. To detect asymptomatic cases, screening programmes for healthcare workers is recommended.

Osteotomía periacetabular en el tratamiento de displasia de cadera mediante técnica mini-invasiva. Nuestros resultados a medio plazo en 131 casos / Periacetabular osteotomy for hip dysplasia treatment through a mini-invasive technique. Our results at mid-term in 131 cases

ANTECEDENTES Y OBJETIVO: La osteotomía periacetabular (OPA) es una técnica utilizada para el tratamiento de la displasia residual, incluso en caderas inestables con cobertura acetabular limitada. El objetivo de este estudio es analizar los resultados funcionales, radiológicos y las complicaciones en pacientes tratados mediante OPA mini-invasiva. MATERIALES Y MÉTODOS: Estudio retrospectivo que analiza 131 casos intervenidos con OPA en nuestro centro. Se determinó de forma prequirúrgica y al final del seguimiento el grado de degeneración articular con la escala de Tönnis, el ángulo de Wiberg, el índice acetabular, el ángulo de cobertura anterior, el espacio articular, las posibles complicaciones y el resultado funcional mediante la escala Non-Arthritic Hip Score. RESULTADOS: La edad media de 32,3±9,5 (DE) años, 102 (77,9%) fueron mujeres y 29 (22,1%) fueron hombres. El seguimiento fue de 7,7±2,8 (DE) años. Se obtuvo una mejora en los parámetros radiológicos entre el momento prequirúrgico y al final del seguimiento, ángulo de Wiberg de+18,5° (18,3° versus 36,8°, IC 95%: 17,3 a 19,7), ángulo de cobertura anterior de+13,5° (26,2° versus 39,7°, IC 95%: 11,6 a 15,4) y el índice acetabular de -11,1° (19,5° versus 8,4°; IC 95%: -12,1 a -10,1). Además, los resultados funcionales con la escala Non-Arthritic Hip Score mejoraron en+31,3 puntos (60,7 prequirúrgico versus 92 último seguimiento posquirúrgico; IC 95%: 28,7 a 33,8). La complicación más frecuente fue la disestesia transitoria del nervio fémoro-cutáneo lateral en 10 casos (7%). CONCLUSIÓN: La osteotomía periacetabular mediante el abordaje mini-invasivo es una técnica reproducible, permite restaurar la cobertura acetabular y proporciona una mejora en las escalas funcionales según confirma nuestra serie

BACKGROUND AND OBJECTIVE: Periacetabular osteotomy (PAO) is an accepted and worldwide technique recognized for residual dysplasia treatment and even in unstable hips with limited acetabular coverage. The aim of this study is to analyse the functional, radiological and complication results in patients treated with mini-invasive PAO. MATERIAL AND METHODS: We performed a retrospective study in which we analysed 131 cases undergoing mini-invasive PAO at our centre. The degree of joint degeneration was evaluated with Tönnis scale, Wiberg angle, acetabular index (AI), anterior coverage angle (AC), joint space, complications and functional outcome with the Non-Arthritic Hip Score (NAHS) were analysed preoperatively and at the end of follow-up. RESULTS: The average age was 32.3±9.5 (SD) years, 102 (77.9%) were female and 29 (22.1%) were male. 7.7±2.8 (SD) years follow up. The radiological parameters improved between the pre-surgical phase and the end of follow-up, Wiberg angle+18.5° (18.3° versus 36.8°, 95% CI 17.3 to 19.7), AC angle+13.5° (26.2° versus 39.7°, 95%CI 11.6 to 15.4) and the AI -11.1° (19.5° versus 8.4°; 95%CI -12.1 to -10,1). In addition, the functional results, with the NAHS scale, improved+31.3 points (60.7 pre-surgical versus 92 at the end of follow-up, 95% CI 28.7 to 33.8). The most common complication was transient lateral femoral cutaneous nerve hypoaesthesia in 10 cases (7%). CONCLUSION: The mini-invasive PAO approach is a reproducible technique, it allows restoration of acetabular coverage and provides an improvement in functional scales as confirmed by our series

Periacetabular osteotomy for hip dysplasia treatment through a mini-invasive technique. Our results at mid-term in 131 cases. / Osteotomía periacetabular en el tratamiento de displasia de cadera mediante técnica mini-invasiva. Nuestros resultados a medio plazo en 131 casos.

BACKGROUND AND OBJECTIVE: Periacetabular osteotomy (PAO) is an accepted and worldwide technique recognized for residual dysplasia treatment and even in unstable hips with limited acetabular coverage. The aim of this study is to analyse the functional, radiological and complication results in patients treated with mini-invasive PAO. MATERIAL AND METHODS: We performed a retrospective study in which we analysed 131 cases undergoing mini-invasive PAO at our centre. The degree of joint degeneration was evaluated with Tönnis scale, Wiberg angle, acetabular index (AI), anterior coverage angle (AC), joint space, complications and functional outcome with the Non-Arthritic Hip Score (NAHS) were analysed preoperatively and at the end of follow-up. RESULTS: The average age was 32.3±9.5 (SD) years, 102 (77.9%) were female and 29 (22.1%) were male. 7.7±2.8 (SD) years follow up. The radiological parameters improved between the pre-surgical phase and the end of follow-up, Wiberg angle+18.5° (18.3° versus 36.8°, 95% CI 17.3 to 19.7), AC angle+13.5° (26.2° versus 39.7°, 95%CI 11.6 to 15.4) and the AI -11.1° (19.5° versus 8.4°; 95%CI -12.1 to -10,1). In addition, the functional results, with the NAHS scale, improved+31.3 points (60.7 pre-surgical versus 92 at the end of follow-up, 95% CI 28.7 to 33.8). The most common complication was transient lateral femoral cutaneous nerve hypoaesthesia in 10 cases (7%). CONCLUSION: The mini-invasive PAO approach is a reproducible technique, it allows restoration of acetabular coverage and provides an improvement in functional scales as confirmed by our series.

Prospective multicentre study on azole resistance in Aspergillus isolates from surveillance cultures in haematological patients in Italy.

OBJECTIVES: This study was conducted to assess the prevalence of azole resistance in Aspergillus isolates from patients with haematological malignancies or who were undergoing haematopoietic stem cell transplantation and to identify the molecular mechanism of resistance. METHODS: In this 28-month prospective study involving 18 Italian centres, Aspergillus isolates from surveillance cultures were collected and screened for azole resistance, and mutations in the cyp51A gene were identified. Resistant isolates were genotyped by microsatellite analysis, and the allelic profiles were compared with those of resistant environmental and clinical isolates from the same geographical area that had been previously genotyped. RESULTS: There were 292 Aspergillus isolates collected from 228 patients. The isolates belonged mainly to the section Fumigati (45.9%), Nigri (20.9%), Flavi (16.8%) and Terrei (4.8%). Three isolates showed itraconazole resistance: Aspergillus fumigatus sensu stricto, Aspergillus lentulus (section Fumigati) and Aspergillus awamori (section Nigri). The itraconazole resistance rates were 1% and 1.48% considering all Aspergillus spp. isolates and the Aspergillus section Fumigati, respectively. The prevalence of azole resistance among all the patients was 1.3%. Among patients harbouring A. fumigatus sensu stricto isolates, the resistance rate was 0.79%. The A. fumigatus isolate, with the TR34/L98H mutation, was genotypically distant from the environmental and clinical strains previously genotyped. CONCLUSIONS: In this study, the Aspergillus azole resistance rate was 1% (3/292). In addition to A. fumigatus sensu stricto, A. lentulus and A. awamori azole-resistant isolates were identified. Therefore, it is important have a correct identification at the species level to address a rapid therapy better, quickly understand the shift towards cryptic species and have an updated knowledge of the local epidemiology.

Respiratory specimens and the diagnostic accuracy of Aspergillus lateral flow assays (LFA-IMMY™): real-life data from a multicentre study.

OBJECTIVES: Proper diagnosis of invasive aspergillosis is challenging because conventional methods lack sensitivity and are complicated by time-consuming incubation processes. To meet the requirement for early diagnosis the new Aspergillus-specific point-of-care test LFA-IMMY™ was evaluated with respect to the ability to accurately detect Aspergillus in bronchoalveolar fluids and sputa, and to clarify the potential of cross-reactivity with other fungal pathogens. METHODS: Respiratory specimens (n = 398) from non-selected patients (n = 390) underwent either fungal microscopy, culture or both before Aspergillus lateral flow assay (LFA-IMMY) testing. RESULTS: For Aspergillus culture- and microscopy-positive samples, sensitivity (48/52) and specificity (44/48) were 92% (95% CI 8.0%-9.7%) and 91% (95% CI 7.9%-9.7%), respectively; cross-reactivity was documented with non-Aspergillus pathogens. CONCLUSION: LFA-IMMY is a reliable diagnostic tool for the detection of Aspergillus in respiratory samples.

A prospective international Aspergillus terreus survey: an EFISG, ISHAM and ECMM joint study.

OBJECTIVES: A prospective international multicentre surveillance study was conducted to investigate the prevalence and amphotericin B susceptibility of Aspergillus terreus species complex infections. METHODS: A total of 370 cases from 21 countries were evaluated. RESULTS: The overall prevalence of A. terreus species complex among the investigated patients with mould-positive cultures was 5.2% (370/7116). Amphotericin B MICs ranged from 0.125 to 32 mg/L, (median 8 mg/L). CONCLUSIONS: Aspergillus terreus species complex infections cause a wide spectrum of aspergillosis and the majority of cryptic species display high amphotericin B MICs.

Direct identification of major Gram-negative pathogens in respiratory specimens by respiFISH® HAP Gram (-) Panel, a beacon-based FISH methodology.

Rapid detection of microorganisms in respiratory specimens is of paramount importance to drive the proper antibiotic regimen to prevent complications and transmission of infections. In the present study, the respiFISH® HAP Gram (-) Panel (miacom diagnostics GmbH, Duesseldorf, Germany) for the etiological diagnosis of hospital-acquired pneumonia was compared with the traditional culture method for the detection of major Gram-negative pathogens in respiratory specimens. respiFISH® combined the classical fluorescence in situ hybridization (FISH) technology with fluorescence-labeled DNA molecular beacons as probes. From September 2011 to January 2012, 165 samples were analyzed: the sensitivity and specificity were 94.39 and 87.93%, respectively. Only six pathogens (3.6%) were not identified with respiFISH®, while seven specimens (3%) provided false-positive results. This beacon-based identification shortens the time to result by at least one work day, providing species-level identification within half an hour. Considering the high sensitivity and specificity and the significant time saving, the introduction of bbFISH® assays could effectively complement traditional systems in microbiology laboratories.

Treatment of chronic pulmonary aspergillosis with voriconazole: review of a case series.

PURPOSE: Chronic pulmonary aspergillosis (CPA) is a rare disease that primarily affects subjects with moderate immunodepression and/or structural alterations in the lung. METHODS: Data for patients with probable CPA were collected over 24 months. Patients with probable CPA received oral voriconazole, and clinical, laboratory and radiological follow-up was performed at 3, 6 and 12 months. RESULTS: 21 patients (mean age 52.4 years) were evaluated. Factors predisposing to CPA were tuberculosis (n = 8), chronic obstructive pulmonary disease (n = 7), corticosteroids (n = 14), chemo- or radio-therapy (n = 6), tracheostomy or endotracheal prosthesis (n = 5), smoking (n = 4), asthma (n = 3), and chronic liver disease (n = 3). Sputum or bronchial aspirate cultures were positive for Aspergillus spp. in 14 cases (66.6 %). (1,3)-ß-D-glucan on serum was positive in 16 cases (76.2 %). Excavated pulmonary thickening was evident in 14 patients (66.6 %) and in 9 of these cases (64.2 %) aspergilloma was present. [(18)F]2-fluoro-2-deoxy-D-glucose-PET-CT was positive in 13/15 patients, and simple aspergilloma was diagnosed after surgical excision in one of the negative cases. All patients were treated with oral voriconazole. Therapy was discontinued due to skin toxicity (n = 3), liver toxicity (n = 2) and severe mental disorder (n = 1). At 12 months' follow-up, nine patients (42.9 %) were considered cured or improved. Seven patients (33.3 %) died during follow-up, mainly due to underlying disease. CONCLUSIONS: A reasonable proportion of patients achieved cure or improvement with voriconazole, but 28.5 % of treated patients had to discontinue therapy because of toxicity. The high mortality makes it difficult to fully assess the real efficacy of voriconazole and to establish the correct duration of therapy.

Interference of confounding factors on the use of (1,3)-beta-D-glucan in the diagnosis of invasive candidiasis in the intensive care unit.

Invasive fungal infections (IFIs) are an increasing problem in intensive care units (ICUs), and conventional diagnostic methods are not always reliable or timely enough to deliver appropriate antimicrobial therapy. The dosage of fungal antigens in serum is a promising diagnostic technique, but several confounding factors, such as treatment with immunoglobulins (Ig), albumin, or antifungals, could interfere with the correct interpretation of the (1,3)-beta-D-glucan (BG) assay. This study assessed the reliability of the BG assay and the influence of timing and dosage of major confounding factors on circulating levels of IFI biomarkers. 267 ICU patients who underwent a BG assay were retrospectively studied. The timing and dosage of albumin, use of azole treatment, and infusions of intravenous IgG, red blood cells, concentrated platelets, and frozen plasma were analyzed to find possible correlations with the BG results. The sensitivity and specificity of the BG assay were calculated. The BG test in serum showed high sensitivity (82.9 %) but low specificity (56.7 %). The optimal cut-off for the test was 95.9 pg/mL. The mean BG level in proven invasive candidiasis was around 400 pg/mL. The only factor that was found to significantly confound (p < 0.05) the diagnostic performance of the BG assay was the administration of more than 30 g of albumin within 2 days prior to BG testing. The BG assay remains a useful diagnostic test in ICU patients and the levels of BG are useful in evaluating the positive predictive value of this biomarker. The only confounding factor in our study was the use of albumin.

A case of Beauveria bassiana keratitis confirmed by internal transcribed spacer and LSU rDNA D1-D2 sequencing.

We describe a case of fungal keratitis due to Beauveria bassiana in a farmer with Fuchs' dystrophy, treated with amphotericin B. Surgery with penetrating keratoplasty was necessary to resolve the lesions. Susceptibility testing and molecular sequencing permitted the identification and treatment of this rare aetiological agent of invasive fungal disease.

Latent tuberculosis infection in patients with chronic plaque psoriasis who are candidates for biological therapy.

BACKGROUND: Screening for latent tuberculosis infection (LTBI) is mandatory in patients with psoriasis prior to biological therapy. OBJECTIVES: To investigate the prevalence of LTBI in patients with psoriasis who are candidates for biological therapy. METHODS: LTBI was investigated in patients with moderate-to-severe psoriasis (n = 243), Crohn disease (n = 64) or rheumatoid arthritis (RA) (n = 56) and in healthcare workers (n = 1683). LTBI diagnosis was based on positive QuantiFERON-B Gold In-Tube (QFT-GIT) in vitro assay without any clinical, radiological or microbiological evidence of active tuberculosis. RESULTS: LTBI was diagnosed in 8.2% of patients with psoriasis, 7% with Crohn disease and 9% with RA, and in 8.8% of healthcare workers (P = 0.9). Patients with psoriasis who also had LTBI (n = 20) received a 9-month prophylaxis with isoniazid (5 mg kg(-1) daily). None of these patients developed active tuberculosis infection after receiving biological therapy (etanercept, adalimumab, infliximab or ustekinumab) for 37 ± 32 weeks (mean ± SD). All patients with psoriasis were retested for LTBI after 31 ± 1.7 months. Five of the 20 patients with LTBI presented QFT-GIT reversion and two patients out of 243 (0.8%) had QFT-GIT conversion and received antibiotic prophylaxis. CONCLUSIONS: The prevalence of LTBI in patients with psoriasis is similar to that in patients with Crohn disease or RA and in healthcare workers. Prophylaxis with isoniazid is effective in preventing tuberculosis reactivation in patients with LTBI receiving biological therapy.

European Confederation of Medical Mycology (ECMM) epidemiological survey on invasive infections due to Fusarium species in Europe.

In order to better understand the epidemiology of fusariosis in Europe, a survey collecting information on the clinical characteristics of the patients infected by Fusarium as well as on the infecting isolates was launched. A total of 76 cases of invasive fusariosis occurring from January 2007 to June 2012 were collected and Fusarium isolates were identified by sequencing the translation elongation factor 1α (TEF) gene. Also, antifungal susceptibility was tested by broth microdilution according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Etest. Disseminated disease was considered proven in 46 cases and probable in 17 cases. Localised infection was seen in 13 cases. Gibberella fujikuroi species complex (SC), including Fusarium verticillioides and F. proliferatum, and F. solani SC were the most frequent aetiology of disseminated and localised infections, respectively. The crude mortality rate was 46 %, the highest associated with F. solani SC (67 %) and F. proliferatum (62.5 %). A wide range of antifungal susceptibilities was observed. Amphotericin B was the most potent antifungal in vitro, and itraconazole the least effective. The azoles exhibited lower minimum inhibitory concentrations (MICs) against F. verticillioides strains, with posaconazole having a slightly better performance, while F. solani SC isolates were resistant to all three azoles tested. The essential agreement between the Etest and the EUCAST method was 100 % for itraconazole and voriconazole, and 96 % for amphotericin B and posaconazole. In conclusion, we confirm that fusariosis is a rare but severe event in Europe, that G. fujikuroi SC is the predominant cause of deep infections and that different species have different antifungal in vitro susceptibility patterns.

Candidemia in intensive care unit: a nationwide prospective observational survey (GISIA-3 study) and review of the European literature from 2000 through 2013.

BACKGROUND: Candida bloodstream infections (BSI) represent an important problem in Intensive Care Units (ICUs). The epidemiology of candidemia is changing with an increase in the proportion of Candida (C.) non-albicans. OBJECTIVES: An Italian 2-year observational survey on ICU was conducted to evaluate the species distribution and possible differences between BSI caused by C. albicans and C. non-albicans. For comparative purposes, we performed a European literature-based review to evaluate distribution and frequency of Candida spp. causing ICU candidemia, during the period 2000-2013. MATERIALS AND METHODS: This laboratory-based survey involved 15 microbiology centers (GISIA-3 study). All candidemia episodes in adult patients were considered. Data were prospectively collected from 2007 to 2008. PubMed was searched for peer-reviewed articles. RESULTS: In total, 462 candidemia episodes were collected. C. albicans accounted for 49.4% of the isolates, followed by C. parapsilosis (26.2%) and C. glabrata (10.4%). Mortality was higher in patients with C. non-albicans than C. albicans (47.3% vs. 32.4 %, p > 0.05). Among risk factors, parenteral nutrition was more common (p = 0.02) in non-albicans candidemia, while surgery was more frequent (p = 0.02) in C. albicans candidemia. Twenty-four relevant articles were identified. C. albicans was the predominant species in almost all studies (range 37.9% -76.3%). C. glabrata was commonly isolated in the German-speaking countries, France, UK and North Europe; C. parapsilosis in Turkey, Greece and Spain. CONCLUSIONS: Although C. non-albicans BSI is increasing, our study shows that C. albicans is still the predominant species in ICU candidemia. There are differences in the epidemiology of Candida BSI among European countries, with a prevalence of C. glabrata and C. parapsilosis in Northern and Southern countries, respectively.

SIMIFF study: Italian fungal registry of mold infections in hematological and non-hematological patients.

PURPOSE: We compared the risk factors, the diagnostic tools and the outcome of filamentous fungal infections (FFIs) in hematological patients (HAEs) and non-hematological patients (non-HAEs). METHODS: Prospective surveillance (2009-2011) of proven and probable FFIs was implemented in 23 Italian hospitals. RESULTS: Out of 232 FFIs, 113 occurred in HAEs and 119 in non-HAEs. The most frequent infection was invasive aspergillosis (76.1 % for HAEs, 56.3 % for non-HAEs), and the localization was principally pulmonary (83.2 % for HAEs, 74.8 % for non-HAEs). Neutropenia was a risk factor for 89.4 % HAEs; the main underlying condition was corticosteroid treatment (52.9 %) for non-HAEs. The distribution of proven and probable FFIs was different in the two groups: proven FFIs occurred more frequently in non-HAEs, whereas probable FFIs were correlated with the HAEs. The sensitivity of the galactomannan assay was higher for HAEs than for non-HAEs (95.3 vs. 48.1 %). The overall mortality rate was 44.2 % among the HAEs and 35.3 % among the non-HAEs. The etiology influenced the patient outcomes: mucormycosis was associated with a high mortality rate (57.1 % for HAEs, 77.8 % for non-HAEs). CONCLUSIONS: The epidemiological and clinical data for FFIs were not identical in the HAEs and non-HAEs. The differences should be considered to improve the management of FFIs according to the patients' setting.

A 1-year prospective survey of candidemia in Italy and changing epidemiology over one decade.

PURPOSE: The aim of this study was to assess the epidemiology of candidemia and antifungal susceptibility profiles of Candida isolates in Italy through a prospective surveillance study and to evaluate changes compared to a previous survey performed in one Italian region (Lombardy) in 1997-1999. METHODS: A prospective laboratory-based surveillance of candidemia was performed in Italy from January to December 2009. For each case a questionnaire was filled in, and the first isolate was collected and tested for in vitro antifungal susceptibility. RESULTS: During our 12-month survey, 467 episodes of candidemia were reported from 34 centres (30 located in Lombardy) and 464 isolates collected. Candida albicans was the predominant species (overall incidence 50.4 %), but the proportion varied considerably from 52.1 % in Lombardy hospitals to 45.2 % hospitals located outside this region. The second most frequent species was C. glabrata in Lombardy and C. parapsilosis in other regions. Comparison of the 1997-1999 and 2009 data on episodes of candidemia in Lombardy revealed a threefold increase in incidence (from 0.38 to 1.19 per 1,000 admissions), aging of infected patients, decline in crude mortality (from 35 to 27.1 %) and an increased proportion of C. glabrata etiology (from 12.8 to 20.3 %). Susceptibility testing confirmed the broad activity of amphotericin B and echinocandins. Decreased susceptibility to fluconazole was found in 24.9 % of the tested isolates. CONCLUSIONS: The results of this latest survey confirm the high rate of candidemia in Italy and show changes in some of the epidemiological tracts, such as aging of infected patients, increased proportion of C. glabrata infections, increased diagnosis in medical wards, and improvement in patients' survival.