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Background: To compare the morbidity and work absenteeism associated with coronavirus disease 2019 (COVID-19) and influenza among health care personnel (HCP) in 2022 to 2023., Methods: We followed 5,752 hospital-based HCP in Greece from November 14, 2022 through May 28, 2023. Symptomatic HCP was tested for SARS-CoV-2 and influenza by real-time polymerase chain reaction and/or rapid antigen detection test. The association between the duration of absenteeism and the type of disease was estimated by multivariable regression models., Results: A total of 734 COVID-19 cases and 93 influenza cases were studied. The mean duration of absence per COVID-19 case was 5.8days compared with a mean of absence of 3.6days per influenza case (P value <.001). Overall, COVID-19 accounted for 4,245days missed during the study period compared with 333days missed due to influenza. Multivariable regression estimates indicated that HCP with COVID-19 had 1.91 more days of absenteeism (95% confidence interval 1.67-2.15) compared with those with influenza, on average., Conclusions: As SARS-CoV-2 becomes endemic, COVID-19 remains the prevalent cause of morbidity and absenteeism among HCP, accounting for considerably more workdays missed compared with influenza. HCP should be up-to-date with COVID-19 booster vaccinations and annual influenza vaccination in order to protect them as well as health care systems from HCP absenteeism., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: To estimate the protection that coronavirus disease 2019 (COVID-19) vaccine doses conferred to hospitalized patients with COVID-19 against adverse outcomes and longer length of stay during the Omicron BA.2 and BA.5 subvariant epidemics in Greece., Methods: The study was conducted from November 2022 to May 2023. Multivariable logistic and negative binomial regression models were applied to estimate the association between any adverse outcomes and length of stay with the number of COVID-19 vaccine doses., Results: We studied 962 patients (median age: 78 years; mean length of stay: 9.2 days), of whom 847 (88.0%) had ≥ 1 comorbidity. Of these, 39 (4.0%) were admitted to the intensive care unit, 44 (4.6%) received invasive mechanical ventilation, and 110 (11.4%) died in hospital. There were 184 (19.1%) unvaccinated patients, 125 (13.0%) with one or two vaccine doses, and 653 (67.9%) with ≥ 3 doses. In multivariable analyses, patients with ≥ 3 doses had lower odds of experiencing any adverse outcomes (adjusted odds ratio: 0.57; 95% confidence interval [CI]: 0.37-0.86) compared with unvaccinated patients. On average, patients with one or two doses and those with ≥ 3 had decreased length of hospital stay (-1.5 days [95% CIs: -2.6 to -0.4] and -2.8 days [95% CIs: -4.1 to -1.4], respectively] compared with unvaccinated patients. Other characteristics consistently associated with adverse outcomes and longer length of stay included older age, having three or more comorbidities compared with none, and being admitted to the hospital two or more weeks post-diagnosis., Conclusions: A history of ≥ 3 vaccine doses conferred significant protection against any adverse outcome and longer length of stay in hospitalized patients with COVID-19., (© 2024 The Author(s).)

Background: To evaluate the influenza-like illness (ILI) and acute respiratory infection (ARI) case definitions in the diagnosis of COVID-19 and influenza in healthcare personnel (HCP)., Methods: We followed a cohort of 5752 HCP from November 2022 to May 2023. Symptomatic HCP were tested for SARS-CoV-2 and influenza by real-time PCR and/or rapid antigen detection test. ILI was defined as the sudden onset of ≥1 systemic symptom and ≥1 respiratory symptom. ARI was defined as the sudden onset of ≥1 respiratory symptom. Patients with respiratory symptoms were grouped either as ILI or as ARI based on the presence of fever, malaise, headache and/or myalgia., Results: Overall, 466 ILI cases and 383 ARI cases occurred. HCP with ILI had an adjusted odds ratio (aOR) of 22.05 [95% confidence interval (CI): 6.23-78.04] to be diagnosed with influenza. HCP with ARI had an aOR of 2.70 (95% CI: 1.88-3.88) to be diagnosed with COVID-19. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ILI for influenza were 96.6%, 49.9%, 18.2%, and 99.2%, respectively. The sensitivity, specificity, PPV, and NPV of ARI for COVID-19 were 51.7%, 73.6%, 84.9%, and 34.8%, respectively. ILI and ARI had an overall correct classification rate of 89.6% and 74.1%, respectively., Conclusion: Our findings support the use of both ILI and ARI case definitions in the diagnosis of influenza and COVID-19 in HCP., Competing Interests: Declaration of competing interest Dr Maltezou received an honorarium from Novavax to participate in a symposium. The authors have no conflict of interest to declare., (Copyright © 2024 Australasian College for Infection Prevention and Control. Published by Elsevier B.V. All rights reserved.)

Background: COVID-19 continues to pose a threat to immunocompromised individuals, even with vaccination. The monoclonal antibodies (mAbs) tixagevimab/cilgavimab (TXG/CIL) provide targeted prophylaxis against SARS-CoV-2 with the benefit of a prolonged half-life. Although approved for COVID-19 prevention, there is limited data on their effectiveness among heavily immunocompromised populations., Methods: We conducted a prospective, observational study at Laiko General Hospital, Athens, Greece, from August to December 2022 to investigate the efficacy of TXG/CIL as a form of pre-exposure prophylaxis in immunocompromised patients. Data on breakthrough SARS-CoV-2 infections were collected over a six-month follow-up period., Results: Of the 375 participants (mean age 61.3 ± 14.1 years; 59.7% male), 76 (20.3%) developed breakthrough SARS-CoV-2 infections, with an incidence of 3.81 cases/100 patient months. Hospitalization was required for 21 patients (5.6%), with a median stay of 14 days. Seven deaths were recorded, with only one attributed to COVID-19. Previous infection (OR 0.46, 95% CI 0.26-0.82) and hybrid immunity (OR 0.52, 95% CI 0.29-0.92) can protect against new infection. Solid organ malignancy significantly increased the risk of severe outcomes among those infected (OR 7.4, 95% CI 2.2-24.7, p = 0.001)., Conclusions: TXG/CIL provides effective prophylaxis against COVID-19 in immunocompromised patients. Future strategies should focus on developing new mAb combinations to address emerging SARS-CoV-2 variants and protect vulnerable populations.

Aim: We assessed the vaccination effectiveness (VE) of a COVID-19 booster vaccine dose and the association between morbidity and absenteeism with COVID-19 booster vaccine receipt among healthcare personnel (HCP) in 2022-2023 in Greece., Methods: We followed 5752 HCP from November 14, 2022 through May 28, 2023 for episodes of absenteeism. Absenteeism for non-infectious causes, pregnancy leave, or annual leave was not recorded. Full vaccination was defined as a primary vaccination series plus one booster dose within the past six months. Multivariable regression models were used to estimate the association of full COVID-19 vaccination with the outcomes of interest., Results: A total of 1029 episodes of absenteeism occurred during the study period (17.9 episodes per 100 HCP). The mean duration of absence per episode was 5.2 days, and the total duration of absence was 5237 days. COVID-19 was diagnosed in 736 (12.8 %) HCP, asymptomatic SARS-CoV-2 infection in 62 (1.1 %) HCP, and influenza in 95 (1.7 %) HCP. Overall, COVID-19, influenza, and asymptomatic SARS-CoV-2 infection accounted for 71.5 %, 9.2 %, and 6.0 % of episodes of absenteeism, respectively. Multivariable regression models indicated that fully vaccinated HCP were absent from work for shorter periods [adjusted odds ratio (aOR): 0.42; 95 % confidence interval (CI): 0.21-0.83], were less likely to develop COVID-19 [aOR: 0.37; 95 % CI: 0.17-0.81)], and were more likely to develop an asymptomatic SARS-CoV-2 infection (aOR: 5.90; 95 % CI: 1.27-27.45). The adjusted full VE against COVID-19 was 62.8 % (95 % CI: 18.6 %-83.0 %)., Conclusions: COVID-19 remains a significant cause of morbidity and absenteeism among HCP. Full COVID-19 vaccination status conferred significant protection against COVID-19 and was associated with shorter periods of absence from work., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Maltezou received an honorarium from Novavax to participate in a symposium., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The coronavirus disease (COVID-19) pandemic has already affected millions of individuals, with increasing numbers of survivors. These data suggest that the pulmonary sequelae of the infection may have an effect on a wide range of individuals. The aim of the present study was to evaluate pulmonary function in patients hospitalized due to COVID-19 three months after hospital discharge. A total of 116 patients, 34 females and 82 males, with a mean age of 57.77±11.45 years, who were hospitalized due to COVID-19, underwent pulmonary function testing three months after their hospital discharge. Of these, 83 (71.6%) patients were hospitalized in the period of alpha variant predominance, 16 (13.8%) in the period of delta variant predominance and 17 (14.6%) in the omicron variant predominance period. The mean value of diffusion capacity for carbon monoxide (DLCO)% predicted (pred) was statistically higher in patients affected by the omicron variant (P=0.028). Abnormal values (<80% pred) of DLCO and total lung capacity (TLC) were observed in 28.4 and 20.7% of the patients, respectively. Active smoking was an independent predictor of abnormal values of forced expiratory volume in 1 sec % pred and TLC% pred [P=0.038; odds ratio (OR): 8.574, confidence interval (CI) 1.124-65.424 and P=0.004, OR: 14.733, CI 2.323-93.429, respectively], age was an independent predictor of abnormal values of forced vital capacity % pred and DLCO% pred (P=0.027, OR: 1.124, CI 1.014-1.246 and P=0.011, OR:1.054, CI 1.012-1.098, respectively); and female sex was an independent predictor of abnormal values of DLCO% pred (P=0.009, OR: 1.124, CI 1.014-1.246). Α significant percentage of hospitalized patients due to COVID-19 pneumonia will develop abnormal pulmonary function, regardless of the SARS-CoV-2 variant., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © Georgakopoulou et al.)

The study aimed to assess the image quality and diagnostic performance of low-dose Chest Computed Tomography (LDCCT) in detecting pulmonary infections in patients with hematologic malignancies. A total of 164 neutropenic patients underwent 256 consecutive CT examinations, comparing 149 LDCCT and 107 Standard-Dose Chest CT (SDCCT) between May 2015 and June 2019. LDCCT demonstrated a 47% reduction in radiation dose while maintaining acceptable image noise and quality compared to SDCCT. However, LDCCT exhibited lower sensitivity in detecting consolidation (27.5%) and ground glass opacity (64.4%) compared to SDCCT (45.8% and 82.2%, respectively) with all the respective p -values from unadjusted and adjusted for sex, age, and BMI analyses being lower than 0.006 and the corresponding Odds Ratios of detection ranging from 0.30 to 0.34. Similar trends were observed for nodules ≥3 mm and ground glass halo in nodules but were not affected by sex, age and BMI. No significant differences were found for cavitation in nodules, diffuse interlobular septal thickening, pleural effusion, pericardial effusion, and lymphadenopathy. In conclusion, LDCCT achieved substantial dose reduction with satisfactory image quality but showed limitations in detecting specific radiologic findings associated with pulmonary infections in neutropenic patients compared to SDCCT.

Remdesivir, a viral RNA polymerase inhibitor, has constituted a key component of therapeutic regimens against the pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Originally approved for administration in hospitalized patients, remdesivir leads to improved outcomes in patients with moderate to severe coronavirus disease 2019 (COVID-19). After proving to be effective in hospitalized patients, its use gained approval in early-stage disease for symptomatic outpatients who are at a high risk of progression to severe disease. The present study is a real-life prospective cohort study involving 143 elderly non-hospitalized patients with SARS-CoV-2 (≥65 years of age) who attended the emergency department of the authors' hospital seeking care for COVID-19 symptoms appearing within the prior 7 days. Eligible patients received intravenous remdesivir at a dose of 200 mg on the first day and 100 mg on days 2 and 3. The efficacy endpoints were set as the need for COVID-19-related hospitalization and all-cause mortality in the following 28 days. A total of 143 patients participated in the study. Of these patients, 118 (82.5%) patients were vaccinated with at least two doses. All patients enrolled completed the 3-day course, with a total of 6 out of 143 patients (4.2%) having a COVID-19-related hospitalization by day 28, and 5 patients (3.5%) succumbing to the disease within the study period. In the univariate Cox regression analysis, the neutrophil-to-lymphocyte ratio and haematological malignancy were identified as predictors of progression to severe disease, and albumin levels, the C-reactive protein-to-albumin ratio (CAR) and haematological malignancy were identified as predictors of 28-day mortality. On the whole, the findings of the present study demonstrated that among the elderly outpatients, a 3-day course of intravenous remdesivir was associated with favourable outcomes., Competing Interests: DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. The other authors declare that they have no competing interests., (Copyright: © Georgakopoulou et al.)

Iron plays an important role in the pathogenesis of infections, including invasive fungal infections (IFIs). Studies suggested that iron overload might represent an additional risk factor for IFIs among patients with hematological malignancies. We conducted a prospective, multi-center study amongst adult patients with newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in transformation to determine whether baseline iron overload as measured using the bone marrow iron store (BMIS) score is an independent risk factor for the development of IFIs. We also measured baseline serum iron and ferritin levels. A total of 98 patients were enrolled (76 with AML) and were followed for 12 months. Twenty-two patients developed IFI during the follow-up period (invasive aspergillosis n = 16, candidemia n = 5, mucormycosis n = 1). A baseline BMIS score ≥ 3 indicated that iron overload was relatively common (38/98 patients, 38%), and its frequency was comparable between patients with no IFIs (31/76, 40.7%) and in those with IFIs (8/22, 36.4%). Univariate analysis showed that only the presence of AML was associated with increased risk for IFIs [OR (95% CI) 7.40 (1.05-325.42)]. Both univariate and multivariate analyses showed that an increased BMIS score (≥3) at baseline was not an independent risk factor for IFIs. Similarly, there was no difference in serum iron and ferritin between the two groups that had similar demographic characteristics. Indices of iron overload were not independent risk factors for IFIs in our cohort of Greek patients with newly diagnosed AML/MDS in transformation.

Background: Nirmatrelvir/ritonavir (NMV/r) and three-day course remdesivir (3RDV) have been approved as early treatments for COVID-19 outpatients not requiring supplemental oxygen. Real-life data on the efficacy of antivirals among immunocompromised patients or directly comparing their effectiveness in preventing hospitalization and/or death are scarce., Methods: Prospective, observational study conducted in a tertiary care hospital, from 1 January 2022 until 15 March 2023, during the prevalence of the Omicron variant. Inverse probability of treatment weighting (IPTW) was used to account for differences between treatment groups., Results: We included 521, mainly immunocompromised (56%), patients in our analysis; 356 (68.3%) received 3RDV and 165 (31.7%) NMV/r. Overall, 15/521 (2.9%) patients met the primary end-point of hospitalization at 30 days (3RDV arm: 10/356, 2.8% vs. NMV/r arm: 5/165, 3%, p = 1). On IPTW-adjusted univariable analysis, the choice of treatment did not affect outcomes. In multivariable logistic regression analysis, we found that one (OR 0.26, 95%CI 0.07-0.99, p = 0.049) or two (OR 0.06, 95%CI 0.01-0.55, p = 0.014) vaccine booster shots reduced the risk for adverse outcomes., Conclusion: In our patient population of high-risk, mainly immunocompromised, vaccinated patients during the prevalence of the Omicron variant, NMV/r and 3RDV were equally effective early treatments for the prevention of hospitalization and/or death.

Surfaces have been implicated in the transmission of pathogens in hospitals. This study aimed to assess the effectiveness of an usnic-acid-containing self-decontaminating coating in reducing microbial surface contamination in tertiary-care hospitals. Samples were collected from surfaces 9 days before coating application, and 3, 10, and 21 days after its application (phases 1, 2, 3, and 4, respectively). Samples were tested for bacteria, fungi, and SARS-CoV2. In phase 1, 53/69 (76.8%) samples tested positive for bacteria, 9/69 (13.0%) for fungi, and 10/139 (7.2%) for SARS-CoV-2. In phase 2, 4/69 (5.8%) samples tested positive for bacteria, while 69 and 139 samples were negative for fungi and SARS-CoV-2, respectively. In phase 3, 3/69 (4.3%) samples were positive for bacteria, 1/139 (0.7%) samples tested positive for SARS-CoV-2, while 69 samples were negative for fungi. In phase 4, 1/69 (1.4%) tested positive for bacteria, while no fungus or SARS-CoV-2 were detected. After the coating was applied, the bacterial load was reduced by 87% in phase 2 (RR = 0.132; 95% CI: 0.108-0.162); 99% in phase 3 (RR = 0.006; 95% CI: 0.003-0.015); and 100% in phase 4 (RR = 0.001; 95% CI: 0.000-0.009). These data indicate that the usnic-acid-containing coating was effective in eliminating bacterial, fungal, and SARS-CoV-2 contamination on surfaces in hospitals.Our findings support the benefit ofan usnic-acid-containing coating in reducing the microbial load on healthcare surfaces.

Aim: We estimated vaccine effectiveness (VE) of full (booster) vaccination against severe outcomes in hospitalized COVID-19 patients during the Delta and Omicron waves., Methods: The study extended from November 15, 2021 to April 17, 2022. Full vaccination was defined as a primary vaccination plus a booster ≥ 6 months later., Results: We studied 1138 patients (mean age: 66.6 years), of whom 826 (72.6 %) had ≥ 1 comorbidity. Of the 1138 patients, 75 (6.6 %) were admitted to intensive care unit (ICU), 64 (5.6 %) received mechanical ventilation, and 172 (15.1 %) died. There were 386 (33.9 %) fully vaccinated, 172 (15.1 %) partially vaccinated, and 580 (51 %) unvaccinated patients. Unvaccinated patients were absent from work for longer periods compared to partially or fully vaccinated patients (mean absence of 20.1 days versus 12.3 and 17.3 days, respectively; p-value = 0.03). Compared to unvaccinated patients, fully vaccinated patients were less likely to be admitted to ICU [adjusted relative risk (ARR: 0.49; 95 % CI: 0.29-0.84)], mechanically ventilated (ARR: 0.43; 95 % CI: 0.23-0.80), and die (ARR: 0.57; 95 % CI: 0.42-0.78), while they were hospitalized for significantly shorter periods (ARR: 0.79; 95 % CI: 0.70-0.89). The adjusted full VE was 48.8 % (95 % CI: 42.7 %-54.9 %) against ICU admission, 55.4 % (95 % CI: 52.0 %-56.2 %) against mechanical ventilation, and 22.6 % (95 % CI: 7.4 %-34.8 %) against death. For patients with ≥ 3 comorbidities, VE was 56.2 % (95 % CI: 43.9 %-67.1 %) against ICU admission, 60.2 % (95 % CI: 53.7 %-65.4 %) against mechanical ventilation, and 43.9 % (95 % CI: 19.9 %-59.7 %) against death., Conclusions: Full (booster) COVID-19 vaccination conferred protection against severe outcomes, prolonged hospitalization, and prolonged work absenteeism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aim: To estimate the incidence, timing and severity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) breakthrough infections in fully vaccinated healthcare personnel (HCP)., Methods: In total, 6496 fully vaccinated HCP were analysed prospectively from 15 th November 2021 to 17 th April 2022. Full coronavirus disease 2019 (COVID-19) vaccination was defined as a complete primary vaccination series followed by a booster dose at least 6 months later., Results: Overall, 1845 SARS-CoV-2 breakthrough infections occurred (28.4 episodes per 100 HCP), of which 1493 (80.9%) were COVID-19 cases and 352 (19.1%) were asymptomatic infections. Of the 1493 HCP with COVID-19, four were hospitalized for 3-6 days (hospitalization rate among HCP with COVID-19: 0.3%). No intubations or deaths occurred. SARS-CoV-2 breakthrough infections occurred at a mean of 16.2 weeks after the last vaccine dose. Multi-variable regression analyses showed that among the 1845 HCP with a breakthrough infection, the administration of a COVID-19 vaccine dose ≥16.2 weeks before the infection was associated with increased likelihood of developing COVID-19 rather than asymptomatic SARS-CoV-2 infection [odds ratio (OR) 1.58, 95% confidence interval (CI) 1.01-2.46; P=0.045] compared with administering a vaccine dose later. The likelihood of developing COVID-19 compared with asymptomatic infection increased by 7% weekly after the last COVID-19 vaccine dose (OR 1.07, 95% CI 1.03-1.11; P=0.001)., Conclusion: SARS-CoV-2 breakthrough infections are common among fully (boosted) vaccinated HCP. However, full COVID-19 vaccination offered considerable protection against hospitalization. These findings may contribute to defining the optimal timing for booster vaccinations. More efficient COVID-19 vaccines that will also confer protection against SARS-CoV-2 infection are needed urgently., (Copyright © 2022 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Osteoarticular mycoses are chronic debilitating infections that require extended courses of antifungal therapy and may warrant expert surgical intervention. As there has been no comprehensive review of these diseases, the International Consortium for Osteoarticular Mycoses prepared a definitive treatise for this important class of infections. Among the etiologies of osteoarticular mycoses are Candida spp., Aspergillus spp., Mucorales, dematiaceous fungi, non-Aspergillus hyaline molds, and endemic mycoses, including those caused by Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides species. This review analyzes the history, epidemiology, pathogenesis, clinical manifestations, diagnostic approaches, inflammatory biomarkers, diagnostic imaging modalities, treatments, and outcomes of osteomyelitis and septic arthritis caused by these organisms. Candida osteomyelitis and Candida arthritis are associated with greater events of hematogenous dissemination than those of most other osteoarticular mycoses. Traumatic inoculation is more commonly associated with osteoarticular mycoses caused by Aspergillus and non-Aspergillus molds. Synovial fluid cultures are highly sensitive in the detection of Candida and Aspergillus arthritis. Relapsed infection, particularly in Candida arthritis, may develop in relation to an inadequate duration of therapy. Overall mortality reflects survival from disseminated infection and underlying host factors.

Aim: We assessed the impact of COVID-19 vaccination status and time elapsed since the last vaccine dose on morbidity and absenteeism among healthcare personnel (HCP) in the context of a mandatory vaccination policy., Methods: We followed 7592 HCP from November 15, 2021 through April 17, 2022. Full COVID-19 vaccination was defined as a primary vaccination series plus a booster dose at least six months later., Results: There were 6496 (85.6 %) fully vaccinated, 953 (12.5 %) not fully vaccinated, and 143 (1.9 %) unvaccinated HCP. A total of 2182 absenteeism episodes occurred. Of 2088 absenteeism episodes among vaccinated HCP with known vaccination status, 1971 (94.4 %) concerned fully vaccinated and 117 (5.6 %) not fully vaccinated. Fully vaccinated HCP had 1.6 fewer days of absence compared to those not fully vaccinated (8.1 versus 9.7; p-value < 0.001). Multivariable regression analyses showed that full vaccination was associated with shorter absenteeism compared to not full vaccination (OR: 0.56; 95 % CI: 0.36-0.87; p-value = 0.01). Compared to a history of ≤ 17.1 weeks since the last dose, a history of > 17.1 weeks since the last dose was associated with longer absenteeism (OR: 1.22, 95 % CI:1.02-1.46; p-value = 0.026) and increased risk for febrile episode (OR: 1.33; 95 % CI: 1.09-1.63; p-value = 0.004), influenza-like illness (OR: 1.53, 95 % CI: 1.02-2.30; p-value = 0.038), and COVID-19 (OR: 1.72; 95 % CI: 1.24-2.39; p-value = 0.001)., Conclusions: The COVID-19 pandemic continues to impose a considerable impact on HCP. The administration of a vaccine dose in less than four months before significantly protected against COVID-19 and absenteeism duration, irrespective of COVID-19 vaccination status. Defining the optimal timing of boosters is imperative., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: Our aim was to estimate vaccination and susceptibility rates against vaccine-preventable diseases among healthcare personnel (HCP) in eight hospitals., Methods: Cross-sectional survey., Results: A total of 1284 HCP participated (physicians: 31.3%, nursing personnel: 36.6%, paramedical personnel: 11.1%, administrative personnel: 13.2%, supportive personnel: 7.3%). Vaccination rates were 32.9% against measles and mumps, 38.1% against rubella, 5.7% against varicella, 9.2% against hepatitis A, 65.8% against hepatitis B, 31.8% against tetanus-diphtheria, 7.1% against pertussis, 60.2% against influenza, and 80.1% against COVID-19. Susceptibility rates were as follows: 27.8% for measles, 39.6% for mumps, 33.4% for rubella, 22.2% for varicella, 86.3% for hepatitis A, 34.2% for hepatitis B, 68.2% for tetanus-diphtheria, and 92.9% for pertussis. Older HCP had higher susceptibility rates against mumps, rubella, varicella, hepatitis A, hepatitis B, tetanus-diphtheria, and pertussis (p-values <0.001 for all). Mandatory vaccinations were supported by 81.85% of HCP., Conclusions: Although most HCPs supported mandatory vaccinations, significant vaccination gaps, and susceptibility rates were recorded. The proportion of susceptible HCP to measles, mumps, rubella, and varicella has increased in the past decade, mostly because of reduction in acquired cases of natural illness. Vaccination programs for HCP should be developed. A national registry to follow HCP's vaccination rates is urgently needed.

Purpose: Our aim was to study patients with diabetes mellitus and SARS-CoV-2-infection diagnosed during the first pandemic wave in Greece., Methods: Cases were retrieved from the national database of SARS-CoV-2 infections., Results: We studied 2624 SARS-CoV-2 infected cases, including 157 with diabetes. Patients with diabetes more often had other comorbidities (68.8 vs. 24.1%; p-value < 0.001). Among patients with diabetes, 149 (94.9%) developed symptomatic disease (COVID-19) compared to 1817 patients (73.7%) without diabetes (p-value < 0.001). A total of 126 patients with diabetes and COVID-19 were hospitalized and 41 died (27.5% case-fatality rate compared to 7.5% among patients without diabetes; p-value < 0.001). Patients with diabetes more often were hospitalized, developed complications, were admitted to the intensive care unit (ICU), received invasive mechanical ventilation, and died compared to patients without diabetes (p-values < 0.001 to 0.002 for all comparisons). Multivariate logistic regression analyses revealed that diabetes, having other comorbidities, and older age were significantly associated with higher risk for hospitalization, ICU admission, invasive mechanical ventilation, and death, and that obesity was significantly associated with higher risk for hospitalization, ICU admission, and mechanical intubation, while female gender protected against these outcomes., Conclusion: COVID-19 is associated with increased rates of serious morbidity and adverse outcome in patients with diabetes and represents a severe illness for them., (© 2022. Hellenic Endocrine Society.)

We studied the third coronavirus disease 2019 (COVID-19) pandemic wave in Athens metropolitan area (3 738 901 inhabitants) through two seroepidemiological surveys. Persons presenting in 12 healthcare facilities across Athens in March and June 2021 were studied (764 and 901, respectively). Immunoglobulin G antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein were measured by a chemiluminescent microparticle immunoassay. In March the seroprevalence rate was 11.6%, meaning that 435 208 residents of Athens had evidence of immunity. The respective values in June were 55.7% and 2 082 568 residents. The highest seroprevalence rates attributed to SARS-CoV-2 infection were recorded in persons <18 years (16.3% in March and 31.6% in June), while immunity was mainly vaccine-induced in persons 18-64 years and >65 years. Infection-attributed immunity also increased in older-age groups. Wide ranges in seroprevalence rates were noted across areas in March and June. The highest seroprevalence rates were recorded in Piraeus (47.2%) and West Attica (37.5%). However, the highest increase (>5 times) occurred in Piraeus and the South Section of Athens, which are among the most densely populated areas in Athens. In both study periods, history of COVID-19 or febrile episode, and having a cohabitant with COVID-19 were associated with increased risk for seropositivity among unvaccinated persons (p values <0.001 for all). Residing in Piraeus, the South Section or West Attica was associated with increased risk for seropositivity in June (p values <0.001). Wide heterogeneity in seroprevalence rates was found across areas in Athens, which is mainly attributed to population density. The impact of population mobility and socioeconomic status should be explored., (© 2021 Wiley Periodicals LLC.)

Aim: Healthcare personnel (HCP) are prioritized for coronavirus disease 2019 (COVID-19) vaccination to protect them and non-disruptive provision of healthcare services. We assessed the impact of the Pfizer-BioNTech vaccine on morbidity and absenteeism among HCP., Methods: We studied 7445 HCP in five tertiary-care hospitals in Greece from November 15, 2020 through April 18, 2021., Results: A total of 910 episodes of absenteeism and 9695 days of absence were recorded during the entire study period. Starting from January 4, 2021, 4823/7445 HCP (64.8%) were fully or partially vaccinated. Overall, 535 episodes of absenteeism occurred from January 4, 2021 through April 18, 2021, including 309 (57.76%) episodes among 2622 unvaccinated HCP and 226 (42.24%) episodes among 4823 vaccinated HCP (11.8 versus 4.7 episodes of absenteeism per 100 HCP, respectively; p-value < 0.001). The mean duration of absenteeism was 11.9 days among unvaccinated HCP compared with 6.9 days among vaccinated HCP (p-value < 0.001). Unvaccinated HCP more frequently developed acute respiratory infection, influenza-like illness, and COVID-19 (p-values < 0.001 for all comparisons). Vaccine effectiveness for fully vaccinated HCP was estimated at 94.16% [confidence interval (CI): 88.50%-98.05%) against COVID-19, 83.62% (CI: 73.36%-90.38%) against SARS-CoV-2 infection (asymptomatic or COVID-19), and 66.42% (CI: 56.86%-74.15%) against absenteeism., Conclusion: The COVID-19 pandemic had a considerable impact on healthcare workforce. The Pfizer-BioNTech vaccine significantly reduced morbidity, COVID-19, absenteeism and duration of absenteeism among HCP during a period of high SARS-CoV-2 circulation in the community. It is expected that HCP vaccination will protect them and healthcare services and contain healthcare costs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: To investigate intention rates to get vaccinated against COVID-19 among healthcare personnel (HCP) in Greece., Methods: Cross-sectional survey., Results: The response rate was 14.5%. Of 1521 HCP with a known profession, 607 (39.9%) were nursing personnel, 480 (31.6%) physicians, 171 (11.2%) paramedical personnel, 72 (4.7%) supportive personnel, and 191 (12.6%) administrative personnel. Overall, 803 of 1571 HCP (51.1%) stated their intention to get vaccinated while 768 (48.9%) stated their intention to decline vaccination. Most HCP (71.3%) who reported intent to get vaccinated noted contributing to the control of the pandemic and protecting their families and themselves as their reasons, while the most common reason for reporting intent to decline vaccination was inadequate information about the vaccines (74.9%), followed by concerns about vaccine safety (36.2%). Logistic regression analysis revealed that the probability of intending to get vaccinated increased with male gender, being a physician, history of complete vaccination against hepatitis B, history of vaccination against pandemic A (H1N1) in 2009-2010, belief that COVID-19 vaccination should be mandatory for HCP, and increased confidence in vaccines in general during the COVID-19 pandemic. The following factors were associated with a lower intention to get vaccinated: no vaccination against influenza the past season, no intention to get vaccinated against influenza in 2020-2021, and no intention to recommend COVID-19 vaccination to high-risk patients., Conclusion: There is an urgent need to built safety perception towards COVID-19 vaccines and raise vaccine uptake rates by HCP, and thus to protect the healthcare workforce and the healthcare services., (Copyright © 2021 Australasian College for Infection Prevention and Control. Published by Elsevier B.V. All rights reserved.)

The incidence of acute coronary events is increased among people living with HIV (PLWH), but there is no risk estimation score, nor a surrogate biomarker able to predict subclinical coronary artery disease (sCAD). We assessed the performance of: (i) Framingham risk score (FRMs), (ii) peripheral (carotid and femoral) artery atheromatosis, and (iii) coronary artery calcium (CACs) score, to detect the presence of sCAD, in PLWH. In a cohort of PLWH free of cardiovascular disease (CVD), we measured sCAD and CACs by computed tomography, calculated FRMs, and assessed carotid/femoral plaques by ultrasound. In 56 participants (age: 49 ± 10 years, men: 88%, FRMs: 7.2 ± 6.9; mean number of carotid/femoral plaques: 1.4 ± 1.5; CACs >0 present in 59%, median CACs 0.9 [IQR 0-22]): (i) minimal sCAD (stenosis 1%-24%; present in 30%) and mild sCAD (25%-49%, 25%) were effectively detected by FRMs, number of plaques, and CACs [area under the curve (AUC) of CACs was better than that of both FRM and plaques, p  < .05]; (ii) moderate sCAD (stenosis 50%-69%; present in 8.9%) was detected by number of plaques and CACs, but similar AUC (0.969 vs. 0.867, respectively, p  = NS); and (iii) severe sCAD (70%-99%, present in only 3 [5.4%]) was detected only by CACs. A high prevalence of sCAD in asymptomatic PLWH free of CVD was detected; CACs is a highly efficient biomarker to detect all grades of sCAD, however, the number of carotid/femoral plaques combined is also a very promising-lower cost and radiation free-surrogate biomarker. Future, larger studies are needed to verify these results.

Introduction: Patients with autoimmune rheumatic diseases (ARDs) are at increased risk for pneumococcal infections and should be vaccinated against Streptococcus pneumoniae. Data on the rates of pneumococcal vaccination among patients with ARDs in Southern Europe are scarce. Here, we estimate the pneumococcal vaccination rate in patients living in Greece with ARDs, explore the patients' awareness regarding vaccination, and try to recognize factors that influence the vaccine uptake., Methods: Between October 2015 and September 2016, a structured questionnaire was provided to all consecutive patients with ARDs attending one outpatient clinic of our department. The survey included parameters concerning patients' demographics, underlying ARD and immunosuppressive medications, other comorbidities, vaccine type, knowledge about infection risk and necessity of vaccination. Univariate and multivariate analyses were performed to study any association of these factors with the vaccination uptake., Results: Overall, 395 patients with ARDs (30.13% aged >65 years and 78.99% female) participated in our survey. The most frequent ARD was rheumatoid arthritis (43.04%); 40.51% of patients were receiving biologic agents and 44.56% steroids. Pneumococcal vaccination rate was 49.37%, while 45.06% of patients have been vaccinated during the last five years and only 8.21% of them had a second pneumococcal vaccine, as per national guidelines. The decision of vaccination was significantly influenced by the patient's age (>65 years) (p < 0.001) and the complete awareness of reasons for being vaccinated (p < 0.001), but not by presence of comorbidities, the type of ARD or administration of a biologic agent. The main reason for no vaccination was that it was not suggested by the caring physician (82.50%)., Conclusions: In our cohort of patients with ARDs the pneumococcal vaccination was suboptimal. Better understanding of the significance of vaccination by the patient and suggestion for vaccination by the caring physician will improve vaccination uptake and optimize the clinical benefits among patients with ARDs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: To assess the impact of an antifungal stewardship (AFS) program on appropriate use, consumption and acquisition costs of antifungals, and on clinical outcomes (in-hospital-mortality, in-hospital-length-of-stay)., Methods: The study was conducted at a 535-bed tertiary-care hospital and had three consecutive periods. A) Observational period (10 months): all antifungal prescriptions were prospectively evaluated. B) Educational intervention to increase the awareness on proper antifungals use. C) Implementation of a non-compulsory AFS program (10 months) based on prospective audit and feedback. Interrupted time series analysis has been used to assess the impact of the intervention., Results: During the pre-interventional period 198 AF prescriptions for 147 patients, have been evaluated compared to 181 prescriptions in 138 patients during the AFS period. Statistical analysis showed a significant immediate drop of inappropriate prescriptions after intervention with a significantly declining trend thereafter, and a significant drop of the total consumption of antifungals immediately after the intervention with a significant declining trend thereafter. All-cause, in-hospital- mortality was stable during the pre-intervention period with a significant declining trend after the AFS program implementation, although no immediate intervention effect could be established. Comparison of pre-and post-interventional periods showed significant reduction in acquisition costs (-26.8%, p<0.001) but no difference regarding the total number of bed-days (107,654 vs. 102,382), and mean length of hospital-stay (5.19 vs. 4.96 days, p=NS)., Conclusions: The implementation of a non-compulsory AFS program resulted in significant improvement in the quality of prescriptions and reduction in antifungals consumption and acquisitions costs, without affecting the overall in-hospital-mortality and mean in-hospital-length-of-stay., (Copyright © 2020. Published by Elsevier Ltd.)

Introduction : Osteoarticular fungal infections (OAFIs) complicate the clinical course of high-risk patients, including immunosuppressed individuals. Their management, however, despite being intricate, is governed by evidence arising from sub-optimal quality research, such as case series. Guidelines are scarce and when present result in recommendations based on low quality evidence. Furthermore, the differences between the management of immunocompromised and immunocompetent patients are not distinct. This is a narrative review after a literature search in PubMed, up to November 2019. Areas covered : The major fungal groups causing osteomyelitis and/or arthritis are Candida spp., Aspergillus spp., non- Aspergillus filamentous fungi, non- Candida yeasts and endemic dimorphic fungi. Their epidemiology is briefly analyzed with emphasis on immunodeficiency and other risk factors. Management of OAFIs includes appropriate antifungal drug therapy (liposomal amphotericin B, triazoles or echinocandins), local surgery and immunotherapy for primary immunodeficiencies. Cessation of immunosuppressive drugs is also mandated. Expert opinion : Management of OAFIs includes affordable and available options and approaches. However, research on therapeutic practices is urgently required to be further improved, due to the rarity of affected patients. Evolution is expected to translate into novel antifungal drugs, less invasive and precise surgical approaches and targeted enhancement of immunoregulatory pathways in defense of challenging fungal pathogens.

Background: Candida tropicalis is a virulent fungal pathogen for which echinocandins are the primary therapy. Emergence of resistance to echinocandins of C. tropicalis carries potentially ominous therapeutic implications., Methods: We describe herein two patients with breakthrough C. tropicalis fungemia during echinocandin therapy, characterize their molecular mechanism of resistance, and systematically review 13 previously reported cases of echinocandin-resistant C. tropicalis bloodstream infections (BSIs) and other diseases., Results: Among these 15 patients with echinocandin-resistant C. tropicalis infections, the median age was 61 years (ages 28-84 years) and 13 (86%) were immunocompromised. Thirteen (86%) of all patients had a history of pervious or concurrent exposure to echinocandins. Isolates of C. tropicalis from 11 cases, including the two index cases, underwent DNA sequencing of the FKS1 gene for mutations known to confer echinocandin resistance. The amino acid substitution Ser654Pro was shown in four cases, while other FKS1 mutations encoded Ser80S/Pro, Phe641Leu, Phe641Ser, Ser80S/Pro substitutions. These mutational events were not associated with collateral increases in minimum inhibitory concentrations to antifungal triazoles and amphotericin B. Overall mortality in patients with echinocandin-resistant C. tropicalis infections was 40%. Among those six patients who died, two received monotherapy with voriconazole, one was treated with fluconazole, one remained on caspofungin, and two were switched to liposomal amphotericin B. Nine patients (60%) survived after being treated with an antifungal agent other than an echinocandin., Conclusions: Emergence of resistance to echinocandins by C. tropicalis, occurs during antifungal therapy, is associated with high mortality, is mediated by a diverse range of FKS1 mutations, retains in vitro susceptibility to triazoles and amphotericin B, and constitutes an emerging threat to patients with hematological malignancies.

Candida osteomyelitis is a debilitating disease that is difficult to diagnose and treat. As there are no animal models or prospective studies for this uncommon infection, little is known about the pathogenesis, diagnosis, or treatment. We therefore sought to establish an animal model for the study of the pathophysiology, diagnostic modalities, and therapeutic interventions of Candida osteomyelitis. We developed a modified version of the Norden rabbit model of tibial osteomyelitis, in which the right tibia was inoculated intraoperatively with different inocula of C. albicans or normal saline as control. On days 7, 14, and 21 after inoculation, the animals underwent bone radiography, 18-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (PET/CT) scan, and blood sampling for blood cultures, blood counts, erythrocyte sedimentation rate, and Candida mannan antigen serum levels. On day 21, animals were euthanized, and infected tibias harvested for culture and histology. Among eight evaluable animals inoculated with 1 × 106 to 1 × 107 cfu, histology and bone cultures established the presence of Candida osteomyelitis in seven, with a host response of neutrophils, mononuclear cells, multinucleate giant cells, fibrosis, and necrosis. Infected animals demonstrated radiological signs of osteomyelitis with significantly increased tracer uptake in 18FDG-PET/CT scans (P < .01) and elevated serum mannan levels (P < .01). All blood cultures were negative. Indices of inflammation were only slightly increased. In conclusion, we report successful establishment of a new animal model of Candida albicans osteomyelitis that may be applicable to advancing our understanding of the pathophysiology, diagnostic modalities, and treatment of this debilitating infection., (© The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

We assessed the value of conventional culture, vial culture, and broad-range PCR of the sonication fluid (SF), individually or in combinations, for the diagnosis of prosthetic joint infection (PJI). We studied 114 consecutive patients (median age:72.5 years, males: 28.07%) undergoing removal of a total knee or hip prosthesis. By non-microbiologic criteria, 87 patients had aseptic failure, and 27 PJI. All patients had periprosthetic tissue culture, sonication of prosthesis, and study of SF by conventional and vial culture, and PCR. Compared to tissue culture, each test was significantly more sensitive and less specific. If only one test was positive, the sensitivity was 88.46% and specificity 64.29%. If all three SF tests were positive, sensitivity, and NPV were decreasing (34.6% and 80.23%), but specificity and PPV were increasing up to 98.57% and 90.9%, respectively, outperforming tissue culture. A triple negative test practically excluded PJI., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The F508del mutation occurs in approximately 3.5% of Caucasian population of Northern Europe. Heterozygotes have increased risk for asthma and reduced pulmonary function. Allergic bronchopulmonary aspergillosis (ABPA) is more common in patients with cystic fibrosis (CF). We aimed to establish the frequency of F508del mutation in adult patients with ABPA., Methods: A retrospective matched case-control study of CF genotyped patients with ABPA seen at the National Aspergillosis Centre was undertaken. Key data were collected retrospectively from medical records, including respiratory comorbidities, total IgE, Aspergillus IgG and IgE, and immunoglobulins. Cystic fibrosis transmembrane regulator (CFTR) gene mutation analysis included multiplex PCR and sequencing., Results: From a cohort of 189 ABPA patients, 156 were screened for common mutations and variants in the CFTR gene. Eighteen were heterozygous for at least one CFTR mutation; 12 (7.7%) were heterozygous for the F508del, notably; 3 were heterozygous for the intron 8 5T variant; and 1 for an intronic variant of uncertain significance, c.3139 + 18C>T. Eight (67%) had asthma, 7 (58%) had CT-defined bronchiectasis, 4 (33%) hypergammaglobulinemia (>16 g/L), 3 (25%) sinusitis and 1 (8%) chronic pulmonary aspergillosis. Eight (67%) had elevated Aspergillus IgG antibodies (42-98 mg/L), and 8 (67%) had total IgE above 1,000 KIU/L. Two individuals heterozygous for the F508del mutation and the TG12T5 variant were diagnosed with CF, leading to a de novo CF discovery rate of 1.3%., Conclusions: In our ABPA patient cohort, the presence of the delta F508 mutation was higher than that seen in general population. Genetic counseling for CFTR genotyping might be appropriate for these patients.

Despite the recent introduction of mold-active agents (posaconazole and isavuconazole), in addition to amphotericin B products, to our armamentarium against mucormycosis, many uncertainties remain for the management of this uncommon opportunistic infection, as there are no data from prospective randomized clinical trials to guide therapy. In this mini-review, we present the current status of treatment options. In view of the heterogeneity of the disease (different types of affected hosts, sites of infection, and infecting Mucorales), mucormycosis management requires an individualized management plan that takes into account the net state of immunosuppression of the host, including comorbidities, certainty of diagnosis, site of infection, and antifungal pharmacological properties.

Invasive fungal infections caused by drug-resistant organisms are an emerging threat to heavily immunosuppressed patients with hematological malignancies. Modern early antifungal treatment strategies, such as prophylaxis and empirical and preemptive therapy, result in long-term exposure to antifungal agents, which is a major driving force for the development of resistance. The extended use of central venous catheters, the nonlinear pharmacokinetics of certain antifungal agents, neutropenia, other forms of intense immunosuppression, and drug toxicities are other contributing factors. The widespread use of agricultural and industrial fungicides with similar chemical structures and mechanisms of action has resulted in the development of environmental reservoirs for some drug-resistant fungi, especially azole-resistant Aspergillus species, which have been reported from four continents. The majority of resistant strains have the mutation TR34/L98H, a finding suggesting that the source of resistance is the environment. The global emergence of new fungal pathogens with inherent resistance, such as Candida auris, is a new public health threat. The most common mechanism of antifungal drug resistance is the induction of efflux pumps, which decrease intracellular drug concentrations. Overexpression, depletion, and alteration of the drug target are other mechanisms of resistance. Mutations in the ERG11 gene alter the protein structure of C-demethylase, reducing the efficacy of antifungal triazoles. Candida species become echinocandin-resistant by mutations in FKS genes. A shift in the epidemiology of Candida towards resistant non-albicans Candida spp. has emerged among patients with hematological malignancies. There is no definite association between antifungal resistance, as defined by elevated minimum inhibitory concentrations, and clinical outcomes in this population. Detection of genes or mutations conferring resistance with the use of molecular methods may offer better predictive values in certain cases. Treatment options for resistant fungal infections are limited and new drugs with novel mechanisms of actions are needed. Prevention of resistance through antifungal stewardship programs is of paramount importance.

Introduction: We studied the relationship between GORD and allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA), or Aspergillus bronchitis., Background: Gastroesophageal reflux disease (GORD) is well known to initiate or exacerbate pulmonary inflammatory conditions, inducing bronchial asthma and chronic obstructive lung disease., Methods: We reviewed four patients referred with elevated Aspergillus serology markers and marked pulmonary symptoms for ABPA, CPA, and Aspergillus bronchitis, and discussed the underlying pathophysiological relationship with GORD. Data were collected retrospectively from medical records included age, gender, predisposing factors for ABPA, chronic pulmonary aspergillosis, or Aspergillus bronchitis; presence of nocturnal reflux, nausea, epigastric pain, Medical Research Council dyspnea scale score, pH manometry data, endoscopic results (ulcers, Barrett's esophagus), treatment of GORD [proton-pump inhibitors (PPIs), surgical operation]; history of smoking, alcohol consumption; concomitant COPD; serological markers (anti-Aspergillus IgG, anti-Aspergillus IgE), and antifungal treatment., Results: Four patients with GORD were studied; following PPIs administration two achieved clinical improvement. One had ABPA, one CPA, and two had Aspergillus bronchitis; median age was 57 years [range 39-71]; males-to-females ratio was 1:3. Serological markers for aspergillosis were: median total IgE antibodies 573 KIU/L [range 13.1-850], median Aspergillus IgE-specific antibodies 1.2 kAU/L [range <0.4-24.7], and median Aspergillus IgG titers 71 mg/L [range 20-119]. Aspergillus fumigatus grew in one sputum sample., Conclusion: Clinicians caring for patients with gastroesophageal reflux disease presenting with elevated Aspergillus IgG or IgE antibodies should maintain a high index of suspicion for this association and proceed to appropriate evaluations, including laryngoscopy and endoscopy, initiating specific PPI-directed therapy when indicated.

Osteomyelitis and arthritis caused by mucormycetes are rare diseases that rank among the most challenging complications in orthopedic and trauma surgery. The aim of this work is to review the epidemiological, clinical, diagnostic, and therapeutic aspects of the osteoarticular mucormycosis with particular emphasis on high-risk patients. A systematic review of osteoarticular mucormycosis was performed using PUBMED and EMBASE databases from 1978 to 2014. Among 34 patients with median age 41 (0.5-73 years), 24 (71%) were males. While 12 (35%) were immunocompromised patients, 14 (41%) had prior surgery, and seven (21%) suffered trauma. Other underlying conditions included diabetes mellitus, hematological malignancies, transplantation, and corticosteroid therapy. The median diagnostic delay from onset of symptoms and signs was 60 (10-180) days. The principal mechanism of the infection was direct inoculation (n = 19; 56%), and in immunocompromised patients was usually hematogenous disseminated. The long bones were infected by trauma or surgery, while a wide variety of bones were involved by hematogenous dissemination. Combined surgery and amphotericin B treatment were implemented in 28 (82%) and eight (23%) had an unfavorable outcome. Osteoarticular mucormycosis occurs most frequently after trauma or surgical procedures. These infections are progressively destructive and more virulent in individuals with impaired immune systems. Early diagnosis, timely administration of amphotericin B, control of underlying conditions, and surgical debridement of infected tissue are critical for successful management of osteoarticular mucormycosis., (© The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aspergillus arthritis is a debilitating form of invasive aspergillosis. Little is known about its epidemiology, clinical manifestations, laboratory features, treatment, and prognosis. Cases of Aspergillus arthritis were reviewed in the English literature from 1967 through 2015 for variables of arthritis with Aspergillus spp. recovered from joint and/or adjacent bone, underlying conditions, symptoms, signs, inflammatory biomarkers, diagnostic imaging, management, and outcome. Among 31 evaluable cases, 87% were males and 13% pediatric. Median age was 50 y (range 1-83 y). Seventeen (55%) patients were immunosuppressed with such conditions as hematological malignancies (26%), corticosteroids (39%), and/or transplantation (26%). Approximately one-half (52%) of patients had hematogenous seeding of the joint, and more than 80% had de novo infection with no prior antifungal therapy. Oligoarticular infection (2-3 joints) occurred in 45% and contiguous osteomyelitis was present in 61%. Clinical manifestations included pain (87%), edema (26%), and limited function (23%), with knees (35%), intervertebral discs (26%), and hips (16%) being most commonly infected. Aspergillus fumigatus constituted 77% of cases followed by Aspergillus flavus in 13%, Aspergillus niger in 3%, and not specified in 7%. Median ESR was 90 mm/hr and median CRP was 3.6 mg/dl. Median synovial fluid WBC was 17,200/μL (7,300-128,000) with 72% PMNs (range 61-92). Osteolysis occurred in 35%, and soft-tissue extension 47%. Nineteen patients (61%) were managed with combined medical and surgical therapy, 10 (32%) with medical therapy only, and 2 (6%) surgery only. Amphotericin B and itraconazole were the most frequently used agents with median duration of therapy of 219 days (range 30-545). Surgical interventions included debridement in 61%, drainage 19%, and amputation 6%. Complete or partial response was achieved in 71% and relapse occurred in 16%. Medical therapy was reinstituted with successful outcome in these patients. Overall survival was 65%. Aspergillus arthritis mainly develops as a de novo infection involving knees and intervertebral disks in immunocompromised patients with localizing symptoms. Contiguous osteomyelitis is frequently observed. Diagnosis is established by synovial fluid culture. Aspergillus arthritis is therapeutically challenging with most patients undergoing surgery and protracted antifungal therapy., (Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Data on the epidemiology of serious fungal infections in Greece are scarce. Our aim was to calculate the burden of serious fungal diseases in Greece. A thorough literature search for papers reporting epidemiological data on serious fungal diseases in Greece was performed. Where no Greek data existed, we used a structured set of assumptions to estimate fungal disease burden, based on specific high-risk populations. Of the 10.8 million population, 85.5 % are adults and 27 % are over 60 years of age. The annual fungal disease estimates are as follows: 142,337 Greek women get recurrent vaginal thrush (2,632 cases/100,000 females); there are 889 cases of esophageal candidiasis (8.2 cases/100,000); annual incidence of Pneumocystis pneumonia is 112 cases; chronic pulmonary aspergillosis prevalence is 386 cases; there are 20,843 patients with allergic bronchopulmonary aspergillosis and 27,744 with severe asthma with fungal sensitization; candidaemia incidence is 541 cases (5.0/100,000); there are 81 cases of Candida peritonitis; invasive aspergillosis occurs in 1,125 patients. According to our calculations, 194,067 individuals (1.79 cases/100,000) in Greece suffer from serious fungal diseases each year. This is the first attempt to determine the burden of fungal diseases in Greece, and provides a crude estimate on its impact on public health.

Background: Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001., Methods: Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0., Results: The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones., Conclusions: Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background.  Candida arthritis is a debilitating form of deeply invasive candidiasis. However, its epidemiology, clinical manifestations, management, and outcome are not well understood. Methods.  Cases of Candida arthritis were reviewed from 1967 through 2014. Variables included Candida spp in joint and/or adjacent bone, underlying conditions, clinical manifestations, inflammatory biomarkers, diagnostic imaging, management, and outcome. Results.  Among 112 evaluable cases, 62% were males and 36% were pediatric. Median age was 40 years (range, <1-84 years). Most patients (65%) were not pharmacologically immunosuppressed. Polyarticular infection (≥3 joints) occurred in 31% of cases. Clinical manifestations included pain (82%), edema (71%), limited function (39%), and erythema (22%) with knees (75%) and hips (15%) most commonly infected. Median erythrocyte sedimentation rate was 62 mm/hr (10-141) and C reactive protein 26 mg/dL (0.5-95). Synovial fluid median white blood cell count was 27 500/µL (range, 100-220 000/µL) with 90% polymorphonuclear neutrophils (range, 24-98). Adjacent osteomyelitis was present in 30% of cases. Candida albicans constituted 63%, Candida tropicalis 14%, and Candida parapsilosis 11%. Most cases (66%) arose de novo, whereas 34% emerged during antifungal therapy. Osteolysis occurred in 42%, joint-effusion in 31%, and soft tissue extension in 21%. Amphotericin and fluconazole were the most commonly used agents. Surgical interventions included debridement in 25%, irrigation 10%, and drainage 12%. Complete or partial response was achieved in 96% and relapse in 16%. Conclusion.  Candida arthritis mainly emerges as a de novo infection in usually non-immunosuppressed patients with hips and knees being most commonly infected. Localizing symptoms are frequent, and the most common etiologic agents are C albicans, C tropicalis, and C parapsilosis. Management of Candida arthritis remains challenging with a clear risk of relapse, despite antifungal therapy.

Background: 18-Fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography ((18)F-FDG PET/CT) scan is useful for diagnosis of osteoarticular infections. Whether (18)F-FDG PET/CT scanning may be used for therapeutic monitoring is not clear. The objective of this study was to develop (18)F-FDG PET/CT scanning for monitoring therapeutic response to antimicrobials in experimental Staphylococcus aureus osteomyelitis., Methods: A total of 22 rabbits were studied. In 20 animals, the right tibia was inoculated intraoperatively with S. aureus. Two control animals were inoculated with normal saline. A needle was placed in the tibia as a foreign body. Infection was allowed to develop for 21 days when (18)F-FDG PET/CT was performed, the needle was removed, and bone specimens were cultured to confirm infection. Antimicrobial therapy with daptomycin was initiated in all successfully infected animals for 1, 3, or 6 weeks. Following completion of treatment, a second (18)F-FDG PET/CT was performed, animals were euthanized, and infected tibias were harvested for quantitative cultures and histology. A positive scan was defined as (18)F-FDG signal activity greater in the infected tibia than that of the contralateral non-infected control tibia. Therapeutic response was measured by the change of (18)F-FDG signal activity in the infected tibia., Results: All successfully infected animals (n = 14), with microbiologically and/or histologically confirmed osteomyelitis, had positive (18)F-FDG PET/CT scans, while the two control animals had negative scans despite the presence of the foreign body [mean maximum standardized uptake value (SUVmax) (±SD) values 2.96 (±0.80) vs. 1 (±1.10), respectively, P = 0.04]. In the 14 successfully infected animals, the mean SUVmax was significantly higher in the infected compared to the uninfected tibia (P < 0.0001). A SUVmax of 1.4, when used as a cutoff for infection, yielded a diagnostic accuracy of 93 %. At the end of treatment, successfully treated animals and saline controls had a negative (18)F-FDG PET/CT scan (n = 4), while animals with persistent infection despite treatment (n = 12) had a positive (18)F-FDG PET/CT scan (SUVmax 1.0-3.0) (p < 0.001). SUVmax values were significantly reduced after 42 days of treatment from 3.15 ± 0.5 (day 7) to 1.71 ± 0.37 (day 42) (p = 0.05)., Conclusions: (18)F-FDG PET/CT scan is a sensitive and specific tool in therapeutic monitoring of experimental foreign-body osteomyelitis.

Background: Anti-thymocyte globulin (ATG) has been used to prevent graft failure/rejection in the setting of allogeneic stem cell transplantation (allo-SCT) for hemoglobinopathies; however, epidemiology data for transplant-related infections in this population are scarce., Method: We retrospectively analyzed the epidemiology of bacterial, fungal, viral, and parasitic infections in a cohort of 105 children and adolescents with β-thalassemia (n = 100) or sickle cell disease (n = 5) who underwent allo-SCT using human leukocyte antigen (HLA)-identical sibling (n = 96) or HLA-compatible unrelated donors (n = 9) in a single institution. All patients received an ATG-based conditioning regimen., Results: The cumulative incidence of cytomegalovirus (CMV) viremia was 45.7% (95% confidence interval [CI] 33-55%), developing at a median of 48 (range 12-142) days without evidence of overt CMV disease. Herpes zoster developed in 8 patients at a median of 12 months post transplant, while 10 patients presented with late onset hemorrhagic cystitis at a median of 35 days post transplant. The cumulative incidence of bacteremia was 17.1% (95% CI 10.6-25%), occurring at a median of 74 (range 24-110) days. No patient developed probable or definite invasive fungal infection. Four deaths were recorded; 2 of them were attributed to infections (toxoplasmosis and Pneumocystis jirovecii pneumonia, respectively)., Conclusion: The rate of infections after allo-SCT, using an ATG-containing preparative regimen, in our population of pediatric patients with hemoglobinopathies is comparable to that reported elsewhere with the use of non-ATG containing regimens., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Data regarding the prevalence and clinical significance of asymptomatic bacteriuria (AB) in women with autoimmune rheumatic disease (ARD) are scarce., Methods: In this prospective, case-control study, consecutive female outpatients with ARD were screened for AB. For each patient, demographics, type, duration, and treatment of underlying ARD, and risk factors for urinary tract infection (UTI), were recorded. Age-matched women with endocrine disease, without any autoimmune disease, not receiving immunosuppressive agents were used as controls. Subjects were followed up for 1 year for the development of symptomatic UTI., Results: Two hundred sixty patients with ARD (mean age, 52.4 [standard deviation {SD}, 14.6] years) and 238 controls (mean age, 51.2 [SD, 16.5] years) were enrolled. The majority of patients with ARD (93.5%; 95% confidence interval [CI], 89.7%-95.9%) were receiving immunosuppressive agents. AB was detected in 24 patients with ARD (9.2%; 95% CI, 6.2%-13.4%) and in 22 controls (9.2%; 95% CI, 5.5%-12.9%) (P = 1.000). The most prevalent pathogen was Escherichia coli (16/24 [66%]). Independent predictors for AB among patients were diabetes (odds ratio [OR], 6.6; P = .008) and a longer ARD duration (>84 months; OR, 4.3; P = .018). During the 1-year follow-up, 9 patients with baseline AB remained persistently bacteriuric, whereas 11 were intermittently bacteriuric. Symptomatic UTI developed in 4 of 24 patients (16.7%; 95% CI, 6.1%-36.5%) with baseline AB vs 29 of 236 (12.3%; 95% CI, 8.6%-17.1%) without AB (P = .522)., Conclusions: In our study, the prevalence of AB among women with ARD was not higher than that of controls, and AB was not associated with higher risk for symptomatic UTI. Risk factors for AB were longer duration of ARD and diabetes., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Current guidelines for treatment of Candida osteoarticular infections (COAIs) recommend a prolonged course of antifungal therapy (AFT) of 6-12 months. Based upon strategies developed at the Hospital for Special Surgery (HSS), we hypothesized that the duration of antifungal therapy may be substantially reduced for management of COAI., Methods: This was a retrospective chart review of cases of COAI treated at the HSS for the past 14 years. COAI was documented by open biopsy and direct culture in all cases. The mean (95% confidence interval, CI) duration of documented follow-up was 39 (16-61) months., Results: Among the 23 cases of COAI, the median age was 62 years (range 22-83 years) with 61% having no underlying condition. Orthopedic appliances, including joint prostheses and fracture hardware, were present in 74% of cases. All patients had COAI as the first proven site of candidiasis. Candida albicans and Candida parapsilosis were the most common species. Hip, knee, foot, and ankle were the most common sites. All patients received aggressive surgical intervention followed by AFT administered for a mean (95% CI) duration of 45 (38-83) days. Systemic AFT consisted principally of fluconazole alone (65%) or in combination with other agents (26%). Adjunctive intraoperative amphotericin B irrigation was used in 35%. Among eight cases of CAOI that required placement of a new prosthetic joint, all were successfully treated. There were no microbiologic failures., Conclusions: Candida osteoarticular infections may be successfully treated with substantially limited durations of AFT when combined with a thorough surgical approach.

The objective of this investigation was to review the clinical manifestations, management, and outcome of osteoarticular infections caused by dimorphic fungi. We exhaustively reviewed reports of bone and joint infections caused by dimorphic fungi published between 1970 and 2012. Underlying conditions, microbiological features, histological characteristics, clinical manifestations, antifungal therapy, and outcome were analyzed in 222 evaluable cases. Among 222 proven cases (median age 41 years [interquartile range (IQR) 26-57]), 73 % had no predisposing condition. Histopathology performed in 128 (57 %) cases and culture in 170 confirmed diagnosis in 63 % and 98 % of the cases, respectively. Diagnosis was obtained from an extra-osteoarticular site in 16 cases. The median diagnostic time was 175 days (IQR 60-365). Sporothrix schenckii was the most frequent pathogen (n = 84), followed by Coccidioides immitis (n = 47), Blastomyces dermatitidis (n = 44), Histoplasma capsulatum (n = 18), Paracoccidioides brasiliensis (n = 16), and Penicillium marneffei (n = 13). Arthritis occurred in 87 (58 %) cases and osteomyelitis in 64 (42 %), including 19 vertebral osteomyelitis. Dissemination was reported in 123 (55 %) cases. Systemic antifungal agents were used in 216 (97 %) patients and in combination with surgery in 129 (60 %). Following the Infectious Diseases Society of America (IDSA) guidelines, a successful initial medical strategy was observed in 97/116 (84 %) evaluable cases. The overall mortality was 6 %, and was highest for P. marneffei (38.5 %). This study demonstrates that dimorphic osteoarticular infections have distinctive clinical presentations, occur predominantly in apparently immunocompetent patients, develop often during disseminated disease, and may require surgical intervention.

In a study of 27,864 patients with haematological malignancies, 40 patients with candidaemia were identified, among whom 21 developed candidaemia while receiving systemic antifungal therapy [breakthrough candidaemia (BTC)]. Demographic, clinical, microbiological and molecular features of these episodes were analysed. Compared with 19 patients with de novo candidaemia, patients with BTC were more likely to have neutropenia (81% vs. 63%), longer median duration of neutropenia (27 days vs. 15 days), hypogammaglobulinaemia (62% vs. 37%) and central venous catheters (CVCs) (86% vs. 68%). The median duration of prior antifungal exposure was 46 days (range 3-108 days). Among the 18 available Candida spp. isolates, 15 (83%) were phenotypically susceptible to the antifungal agent that the patient was receiving. Emergence of resistance was the mechanism leading to BTC in three cases of patients receiving echinocandins. Other possible mechanisms of BTC were (i) elevated (≥2) minimum lethal concentration/minimum inhibitory concentration (MLC/MIC) ratio (reduced ability for a fungicidal agent to kill a fungal pathogen) in all patients receiving amphotericin B and (ii) elevated MLC/MIC ratios in all Candida parapsilosis isolates with MICs≤1 μg/mL to echinocandins. DNA sequencing of the hotspot 1 region of the fks1 and fks2 genes in seven different isolates of C. parapsilosis group demonstrated P660A in Fks1 but no polymorphisms in fks2. In conclusion, mechanisms for BTC in the setting of prolonged neutropenia may be host-based (hypogammaglobulinaemia and CVC) and pathogen-based. CLSI interpretive breakpoints do not reliably predict BTC in patients with haematological malignancies and warrant further investigation., (Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Background: The epidemiology, pathogenesis, diagnosis, and management of Aspergillus osteomyelitis are not well understood., Methods: Protocol-defined cases of Aspergillus osteomyelitis published in the English literature were reviewed for comorbidities, microbiology, mechanisms of infection, clinical manifestations, radiological findings, inflammatory biomarkers, antifungal therapy, and outcome., Results: Among 180 evaluable patients, 127 (71%) were males. Possible predisposing medical conditions in 103 (57%) included pharmacological immunosuppression, primary immunodeficiency, and neutropenia. Seventy-three others (41%) had prior open fracture, trauma or surgery. Eighty (44%) followed a hematogenous mechanism, 58 (32%) contiguous infections, and 42 (23%) direct inoculation. Aspergillus osteomyelitis was the first manifestation of aspergillosis in 77%. Pain and tenderness were present in 80%. The most frequently infected sites were vertebrae (46%), cranium (23%), ribs (16%), and long bones (13%). Patients with vertebral Aspergillus osteomyelitis had more previous orthopedic surgery (19% vs 0%; P = 0.02), while those with cranial osteomyelitis had more diabetes mellitus (32% vs 8%; P = 0.002) and prior head/neck surgery (12% vs 0%; P = 0.02). Radiologic findings included osteolysis, soft-tissue extension, and uptake on T2-weighted images. Vertebral body Aspergillus osteomyelitis was complicated by spinal-cord compression in 47% and neurological deficits in 41%. Forty-four patients (24%) received only antifungal therapy, while 121 (67%) were managed with surgery and antifungal therapy. Overall mortality was 25%. Median duration of therapy was 90 days (range, 10-772 days). There were fewer relapses in patients managed with surgery plus antifungal therapy in comparison to those managed with antifungal therapy alone (8% vs 30%; P = 0.006)., Conclusions: Aspergillus osteomyelitis is a debilitating infection affecting both immunocompromised and immunocompetent patients. The most common sites are vertebrae, ribs, and cranium. Based upon this comprehensive review, management of Aspergillus osteomyelitis optimally includes antifungal therapy and selective surgery to avoid relapse and to achieve a complete response., (Copyright © 2013 The British Infection Association. All rights reserved.)

Invasive candidiasis is a life-threatening infection in patients with haematological malignancies. The objective of our study was to determine the incidence, microbiological characteristics and clinical outcome of candidaemia among hospitalized adult patients with haematological malignancies. This is a population-based, prospective, multicentre study of patients ≥ 18 years admitted to haematology and/or haematopoietic stem cell transplantation units of nine tertiary care Greek hospitals from January 2009 through to February 2012. Within this cohort, we conducted a nested case-control study to determine the risk factors for candidaemia. Stepwise logistic regression was used to identify independent predictors of 28-day mortality. Candidaemia was detected in 40 of 27,864 patients with haematological malignancies vs. 967 of 1,158,018 non-haematology patients for an incidence of 1.4 cases/1000 admissions vs. 0.83/1000 respectively (p <0.001). Candidaemia was caused predominantly (35/40, 87.5%) by non-Candida albicans species, particularly Candida parapsilosis (20/40, 50%). In vitro resistance to at least one antifungal agent was observed in 27% of Candida isolates. Twenty-one patients (53%) developed breakthrough candidaemia while receiving antifungal agents. Central venous catheters, hypogammaglobulinaemia and a high APACHE II score were independent risk factors for the development of candidaemia. Crude mortality at day 28 was greater in those with candidaemia than in control cases (18/40 (45%) vs. 9/80 (11%); p <0.0001). In conclusion, despite antifungal prophylaxis, candidaemia is a relatively frequent infection associated with high mortality caused by non-C. albicans spp., especially C. parapsilosis. Central venous catheters and hypogammaglobulinaemia are independent risk factors for candidaemia that provide potential targets for improving the outcome., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

Invasive fungal infections are important causes of morbidity and attributable mortality in neutropenic patients with hematological malignancies, myelodysplasia, and aplastic anemia. Successful risk-based strategies can be implemented for prophylaxis, empirical therapy, and preemptive therapy for the prevention and early treatment of invasive fungal infections in neutropenic hosts. The use of echinocandins for invasive candidiasis and voriconazole for invasive aspergillosis has significantly improved outcome. Recent studies demonstrate, however, that resistant fungal pathogens may emerge during the course of these antifungal interventions. Although triazole-resistant Candida spp. have been well described as causes of breakthrough candidemia, other organisms now pose a similar threat. Such organisms include echinocandin-resistant Candida glabrata and Candida parapsilosis species complex. The Mucorales, Fusarium spp., and Scedosporium spp. may emerge in the setting of voriconazole prophylaxis. The challenges of these emerging pathogens underscore the need for the development of new antifungal agents and strategies.

Members of the order Mucorales are emerging invasive molds that cause infections in immunocompromised patients. However, little is known about the relation between different species of Mucorales and their virulence in invasive pulmonary mucormycosis. Based upon our earlier epidemiological studies, we hypothesized that Cunninghamella bertholletiae would demonstrate increased virulence. Therefore, we studied the relative virulence of C. bertholletiae (CB), Rhizopus oryzae (RO), R. microsporus (RM), and Mucor circinelloides (MC) in experimental invasive pulmonary mucormycosis in persistently neutropenic rabbits in relation to the fungi in vitro sporangiospore germination rate and hyphal metabolic activity. Rabbits infected with CB demonstrated (1) higher lung weights in comparison to RM (P ≤ 0.05), RO and MC (P ≤ 0.001), (2) pulmonary infarcts in comparison to RO and MC (P ≤ 0.001), (3) tissue fungal burden (CFU/g) vs. MC (P ≤ 0.001), and (4) the lowest survival of 0% (0/18), in comparison to 16% (3/18, P ≤ 0.01) of RM, 81% (21/26) of RO, and 83% (15/18) of MC-infected rabbits (P ≤ 0.001). Serum PCR concentration-time-curve showed the greatest amplitude for CB. Virulence correlated directly with sporangiospore germination rate at 4 h among species, i.e., CB (67-85%) > RM (14-56%) > RO (4-30%) > MC (0%), and hyphal metabolic activity, i.e., CB (1.22-1.51) > MC (0.54-0.64) = RM (0.38-0.41) = RO (0.37-0.59). C. bertholletiae was significantly more virulent in experimental invasive pulmonary mucormycosis than R. microsporus, R. oryzae, and M. circinelloides. In vivo virulence correlated with species-dependent differences of in vitro germination rate and hyphal metabolic activity.

We present 2 cases of HIV-related cryptococcal meningitis, persisting after 3 and 9 months, respectively, of standard treatment. Both patients were treated successfully with a salvage regimen consisting of the combination of liposomal amphotericin B (3 mg/kg), intravenous voriconazole, and subcutaneous recombinant interferon γ-1b (200 μg thrice weekly). Voriconazole was administered at an increased dose (5 mg/kg, twice daily) to overcome interactions with co-administered ritonavir. In both patients, resolution of clinical signs and symptoms, as well as sterilization of cerebrospinal fluid cultures occurred after 10 weeks of salvage therapy. No major side effects were encountered. At the end of treatment, both patients were placed on maintenance therapy with oral fluconazole; no recurrence has been observed after 4 years of follow-up., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The epidemiology, pathogenesis, clinical manifestations, management, and outcome of Candida osteomyelitis are not well understood., Methods: Cases of Candida osteomyelitis from 1970 through 2011 were reviewed. Underlying conditions, microbiology, mechanisms of infection, clinical manifestations, antifungal therapy, and outcome were studied in 207 evaluable cases., Results: Median age was 30 years (range, ≤ 1 month to 88 years) with a >2:1 male:female ratio. Most patients (90%) were not neutropenic. Localizing pain, tenderness, and/or edema were present in 90% of patients. Mechanisms of bone infection followed a pattern of hematogenous dissemination (67%), direct inoculation (25%), and contiguous infection (9%). Coinciding with hematogenous infection, most patients had ≥2 infected bones. When analyzed by age, the most common distribution of infected sites for adults was vertebra (odds ratio [OR], 0.09; 95% confidence interval [CI], .04-.25), rib, and sternum; for pediatric patients (≤18 years) the pattern was femur (OR, 20.6; 95% CI, 8.4-48.1), humerus, then vertebra/ribs. Non-albicans Candida species caused 35% of cases. Bacteria were recovered concomitantly from 12% of cases, underscoring the need for biopsy and/or culture. Candida septic arthritis occurred concomitantly in 21%. Combined surgery and antifungal therapy were used in 48% of cases. The overall complete response rate of Candida osteomyelitis of 32% reflects the difficulty in treating this infection. Relapsed infection, possibly related to inadequate duration of therapy, occurred among 32% who ultimately achieved complete response., Conclusions: Candida osteomyelitis is being reported with increasing frequency. Localizing symptoms are usually present. Vertebrae are the most common sites in adults vs femora in children. Timely diagnosis of Candida osteomyelitis with extended courses of 6-12 months of antifungal therapy, and surgical intervention, when indicated, may improve outcome.

This review focuses on sinus, sino-orbital, and rhinocerebral infection caused by the Mucorales. As the traditional term of "rhinocerebral" mucormycosis omits the critical involvement of the eye, the more comprehensive term as rhino-orbital-cerebral mucormycosis (ROCM) is used. The most common underlying illnesses of ROCM are diabetes mellitus, hematological malignancies, hematopoietic stem cell transplantation, and solid organ transplantation. Sporangiospores are deposited in the nasal turbinates and paranasal sinuses in immunocompromised patients. Qualitative and quantitative abnormalities of neutrophils, monocytes and macrophages increase the risk for development of mucormycosis. Altered iron metabolism also is a critical factor in the pathogenesis of patients with diabetes mellitus who are at risk for ROCM. Angioinvasion with thrombosis and tissue necrosis is a key pathophysiological feature of human Mucorales infection. The ethmoid sinus is a critical site from which sinus mucormycosis may extend through the lamina papyracea into the orbit, extraocular muscles, and optic nerve. The brain may be seeded by invasion of the ethmoidal and orbital veins, which drain into the cavernous sinuses. Diplopia and ophthalmoplegia may be the earliest manifestations of cavernous sinus syndrome before changes are apparent on diagnostic imaging modalities. Negative diagnostic imaging does not exclude cavernous sinus mucormycosis. Mucormycosis of the maxillary sinus has a constellation of clinical features that are different from that of ethmoid sinus mucormycosis. A painful black necrotic ulceration may develop on the hard palate, indicating extension from the maxillary sinus into the oral cavity. Orbital apex syndrome is an ominous complication of mucormycosis of the orbit. Once within the orbital compartment, organisms may extend posteriorly to the optic foramen, where the ophthalmic artery, ophthalmic nerve and optic nerve are threatened by invasion, edema, inflammation and necrosis. Early diagnosis of sinus mucormycosis is critical for prevention of extension to orbital and cerebral tissues. Optimal therapy requires a multidisciplinary approach that relies on prompt institution of appropriate antifungal therapy with amphotericin B, reversal of underlying predisposing conditions, and, where possible, surgical debridement of devitalized tissue. Outcomes are highly dependent upon the degree of immunosuppression, site and extent of infection, timeliness of therapy, and type of treatment provided. New modalities for early diagnosis and therapeutic intervention are critically needed for improved outcome of patients with ROCM.