Hybrid immunity to SARS-CoV-2 in patients with chronic lymphocytic leukemia.

OBJECTIVE: Preventing severe COVID-19 remains a priority globally, particularly in the immunocompromised population. As shown in healthy individuals, immunity against SARS-CoV-2 can be yielded by previous infection, vaccination, or both (hybrid immunity). The objective of this observation study was to investigate hybrid immunity in patients with chronic lymphocytic leukemia (CLL). METHODS/RESULTS: Blood samples of six patients with CLL were collected 55 days after fourth COVID-19 vaccination. All patients had a SARS-CoV-2 infection within 12 months before the second booster (fourth vaccination). SARS-CoV-2 spike receptor binding domain (RBD)-specific IgG antibodies were detectable in 6/6 (100.0%) CLL patients after four compared to 4/6 (66.7%) after three vaccinations. The median number of SARS-CoV-2 spike-specific T cells after repeated booster vaccination plus infection was 166 spot-forming cells (SFC) per million peripheral blood mononuclear cells. Overall, 5/5 (100%) studied patients showed a detectable increase in T cell activity. CONCLUSION: Our data reveal an increase of cellular and humoral immune response in CLL patients after fourth COVID-19 vaccination combined with SARS-CoV-2 infection, even in those undergoing B cell-depleting treatment. Patients with prior vaccination failure now show a specific IgG response. Future research should explore the duration and effectiveness of hybrid immunity considering various factors like past infection and vaccination rates, types and numbers of doses, and emerging variants.

The Cologne ECMM Excellence Center: A Two-Year Analysis of External Consultation Service for Invasive Fungal Infections.

The European Confederation of Medical Mycology (ECMM), formed due to the surge in invasive fungal infections (IFI), initiated the Excellence Centers program in 2016 to guide stakeholders to leading medical mycology sites. This report focuses on the Cologne ECMM Excellence Center, recognized with Diamond status for active global involvement in 2017. The center offers free consultation via email and phone, responding within 24 h for life-threatening IFI, collecting data on origin, pathogens, infection details, and more. Over two years, 189 requests were received globally, predominantly from Germany (85%), mainly involving Aspergillus spp., Mucorales, and Candida spp. Fungal mixed infections occurred in 4% of cases. The center's service effectively addresses IFI challenges, advocating for a comprehensive study encompassing all ECMM Excellence Centers to enhance global mycological care. Proactive expansion of consultancy platforms is crucial, with future analyses needed to assess expert advice's impact on patient outcomes.

[Innovative therapies for treatment of invasive fungal diseases]. / Invasive Mykosen ­ Innovative Therapien.

Invasive fungal diseases (IFD) are difficult to treat and pose a significant threat to immunocompromised individuals. Current antifungal agents face limitations, including antifungal resistance and adverse effects. This review aims to give a comprehensive overview of emerging treatment strategies.Novel drugs in development are Ibrexafungerp, an orally available triterpenoid inhibiting glucan synthesis, and Rezafungin representing the echinocandins with extended half-life and improved tissue penetration, both recently licensed for certain indications. Fosmanogepix targets glycosylphosphatidylinositol biosynthesis, while Olorofim, an orotomide, inhibits fungal nucleic acid synthesis, both currently assessed in advanced clinical trials.Immunotherapeutic approaches include immune checkpoint inhibitors to enhance immune response in immunosuppressed individuals and fungal-specific allogeneic CAR-T cell therapy. For prophylactic purpose in high-risk populations to develop IFD, monoclonal antibodies against different virulence factors of Candida spp. have been discovered but are not yet seen in clinical trials. Vaccines against distinct fungal antigens as well as pan fungal vaccines to prevent IFD are under development in preclinical stages, notably for Candida spp., Cryptococcus spp., and Aspergillus spp., however, their clinical value is still discussed.In summary, major advances to treat IFD have been observed, but challenges for their establishment in the clinical routine persist.

Primary prophylaxis of invasive fungal diseases in patients with haematological malignancies: 2022 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO).

Patients with haematological malignancies (HM) are at high risk of developing invasive fungal disease (IFD) with high morbidity and attributable mortality. We reviewed data published until September 2021 to update the 2017 antifungal prophylaxis recommendations of the German Society of Haematology and Medical Oncology (DGHO). The strong recommendation to administer antifungal prophylaxis in patients with HM with long-lasting neutropenia, i.e. <500 cells/µL for >7 days remains unchanged. Posaconazole remains the drug of choice for mould-active prophylaxis in these patients. Novel treatment options in HM, such as CAR-T-cell treatment or novel targeted therapies for acute myeloid leukaemia (AML) were considered, however, data are insufficient to give general recommendations for routine antifungal prophylaxis in these patients. Major changes regarding specific recommendations compared to the 2017 edition are the now moderate instead of mild support for the recommendations of isavuconazole and voriconazole. Furthermore, published evidence on micafungin allows recommending it at moderate strength for its use in HM. For the first time we included recommendations for non-pharmaceutical measures regarding IFD, comprising the use of high-efficiency particulate air (HEPA) filters, smoking, measures during construction work and neutropenic diets. We reviewed the impact of antifungal prophylaxis with triazoles on drug-drug interactions with novel targeted therapies that are metabolized via cytochrome p450 where triazoles inhibit CYP3A4/5. The working group recommends reducing the dose of venetoclax when used concomitantly with strong CYP3A4 inhibiting antifungals. Furthermore, we reviewed data on the prophylactic use of novel antifungal agents. Currently there is no evidence to support their use in a prophylactic setting in clinical practice.

Increasing influenza vaccination coverage in healthcare workers: analysis of an intensified on-site vaccination campaign during the COVID-19 pandemic.

PURPOSE: Influenza infections have substantial impact on healthcare institutions. While vaccination is the most effective preventive measure against influenza infection, vaccination coverage in healthcare workers is low. The study investigates the impact of an intensified influenza vaccination campaign in a maximum-care hospital on influenza vaccination coverage in healthcare workers during the COVID-19 pandemic in 2020/21. METHODS: Building on findings from our previously published review Schumacher et al. (Infection 49(3): 387, 2021), an intensified influenza vaccination campaign comprising a mobile vaccination team providing on-site vaccination and vaccination at a recurring central vaccination site in addition to promotional measures was performed and analysed regarding vaccination coverage. A survey querying vaccination motivation was performed. Campaign strategies and vaccination coverage of influenza seasons between 2017/18 and 2019/20 were analysed. RESULTS: The influenza vaccination campaign 2020/21 led to a significant 2.4-fold increase yielding an overall vaccination coverage of 40% among healthcare workers. A significant increase in vaccination coverage was observed across all professional fields; especially among nurses, a 2.7-fold increase, reaching a vaccination coverage of 48%, was observed. The COVID-19 pandemic positively influenced vaccination decision in 72% of first time ever or first time in over ten years influenza vaccinees. Vaccination coverage during prior vaccination campaigns focusing on educational measures did not exceed 17%. CONCLUSION: A mobile vaccination team providing on-site vaccination and vaccinations at a central vaccination site in addition to promotional measures can be implemented to increase influenza vaccination coverage in healthcare workers. Our concept can inform influenza and other vaccination campaigns for healthcare workers.

Harmonized procedure coding system for surgical procedures and analysis of surgical site infections (SSI) of five European countries.

BACKGROUND: The use of routine data will be essential in future healthcare research. Therefore, harmonizing procedure codes is a first step to facilitate this approach as international research endeavour. An example for the use of routine data on a large scope is the investigation of surgical site infections (SSI). Ongoing surveillance programs evaluate the incidence of SSI on a national or regional basis in a limited number of procedures. For example, analyses by the European Centre for Disease Prevention (ECDC) nine procedures and provides a mapping table for two coding systems (ICD9, National Healthcare Safety Network [NHSN]). However, indicator procedures do not reliably depict overall SSI epidemiology. Thus, a broader analysis of all surgical procedures is desirable. The need for manual translation of country specific procedures codes, however, impedes the use of routine data for such an analysis on an international level. This project aimed to create an international surgical procedure coding systems allowing for automatic translation and categorization of procedures documented in country-specific codes. METHODS: We included the existing surgical procedure coding systems of five European countries (France, Germany, Italy, Spain, and the United Kingdom [UK]). In an iterative process, country specific codes were grouped in ever more categories until each group represented a coherent unit based on method of surgery, interventions performed, extent and site of the surgical procedure. Next two ID specialist (arbitrated by a third in case of disagreement) independently assigned country-specific codes to the resulting categories. Finally, specialist from each surgical discipline reviewed these assignments for their respective field. RESULTS: A total number of 153 SALT (Staphylococcus aureus Surgical Site Infection Multinational Epidemiology in Europe) codes from 10 specialties were assigned to 15,432 surgical procedures. Almost 4000 (26%) procedure codes from the SALT coding system were classified as orthopaedic and trauma surgeries, thus this medical field represents the most diverse group within the SALT coding system, followed by abdominal surgical procedures with 2390 (15%) procedure codes. CONCLUSION: Mapping country-specific codes procedure codes onto to a limited number of coherent, internally and externally validated codes proofed feasible. The resultant SALT procedure code gives the opportunity to harmonize big data sets containing surgical procedures from international centres, and may simplify comparability of future international trial findings. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov under NCT03353532 on November 27th, 2017.

Validation of the EQUAL Aspergillosis Score by analysing guideline-adherent management of invasive pulmonary aspergillosis.

OBJECTIVES: To investigate the diagnosis and treatment standards at the University Hospital of Cologne, Germany, by applying the EQUAL Aspergillosis Score to invasive pulmonary aspergillosis (IPA) patients. METHODS: The charts of 103 patients with probable or proven IPA at the University Hospital of Cologne were reviewed and the score retrospectively applied to all patients. RESULTS: Patients were stratified into two groups according to the underlying disease: a haematology group (n = 76, 73.8%) and a non-haematology group (n = 27, 26.2%). While the haematology group attained 67.8% of achievable score points (median: 15; IQR: 13-18; range: 8-25), the non-haematology group reached 48.4% (median: 12 points; IQR: 9-14; range: 4-18) (P < 0.001). Regarding diagnostics, haematological patients achieved 81.3% of achievable points (median: 7; IQR: 8-10; range: 3-13) and non-haematological 56.3% (median: 7; IQR: 5-9; range: 3-11). Concerning treatment, haematological patients gained 86.3% (median: 5; IQR: 5-5; range: 0-5) and non-haematological 68.1% (median: 5; IQR: 0-5; range: 0-5) of achievable points. Among the haematological patients with versus those without mould-active prophylaxis, 90 day mortality was 46.0% and 59.3% (P = 0.004), respectively. Guideline adherent management of IPA was observed in 31.1% of cases (39.5% in haematological patients and 7.4% in non-haematological). CONCLUSIONS: The EQUAL Aspergillosis Score is more suitable for evaluation of management of haematological patients compared with those without such underlying disease. In both groups there was no correlation between score points and survival. Larger prospective studies may be suitable to correlate outcome and score. A revision of the score should be considered based on the data presented.

Central venous catheter-related infections in hematology and oncology: 2020 updated guidelines on diagnosis, management, and prevention by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO).

Cancer patients frequently require central venous catheters for therapy and parenteral nutrition and are at high risk of central venous catheter-related infections (CRIs). Moreover, CRIs prolong hospitalization, cause an excess in resource utilization and treatment cost, often delay anti-cancer treatment, and are associated with a significant increase in mortality in cancer patients. We therefore summoned a panel of experts by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) and updated our previous guideline on CRIs in cancer patients. After conducting systematic literature searches on PubMed, Medline, and Cochrane databases, video- and meeting-based consensus discussions were held. In the presented guideline, we summarize recommendations on definition, diagnosis, management, and prevention of CRIs in cancer patients including the grading of strength of recommendations and the respective levels of evidence. This guideline supports clinicians and researchers alike in the evidence-based decision-making in the management of CRIs in cancer patients.

Increasing influenza vaccination coverage in healthcare workers: a review on campaign strategies and their effect.

PURPOSE: Increasing influenza vaccination coverage in healthcare workers is a challenge. Especially during the ongoing COVID-19 pandemic, high vaccination coverage should be attained. This review analyzed strategies to increase influenza vaccination coverage in healthcare workers. METHODS: A literature search using PubMed was conducted and 32 publications on influenza vaccination campaigns for healthcare workers were reviewed for key interventions and resulting vaccination coverage. RESULTS: Among key interventions analyzed, mandatory vaccination policies or multifaceted campaigns including a vaccinate-or-wear-a-mask policy as well as mandatory declination reached vaccination coverage in healthcare workers of over 90%. Although campaigns solely based on education and promotion or on-site-vaccination did not regularly exceed an absolute vaccination coverage of 40%, a substantial relative increase in vaccination coverage was reached by implementation of these strategies. CONCLUSION: Mandatory vaccination policies are effective measures to achieve high overall vaccination coverage. In clinics where policies are infeasible, multifaceted campaigns comprising on-site vaccination, vaccination stands and educational and promotional campaigns as well as incentives should be implemented. Lessons learned from influenza campaigns could be implemented in future SARS-CoV-2 vaccination campaigns.

[Vaccines against COVID-19]. / Impfstoffe gegen COVID-19.

The ongoing COVID-19 pandemic represents an emergency situation of devastating proportions. To mitigate its effects, several safe and effective vaccines have been developed in a very short period of time. Currently, four vaccines have been approved by the European Medicines Agency (EMA) and are in use in Germany. These include two mRNA vaccines and two vector-based vaccines. They all show very good protective efficacy, especially against severe courses of disease and can significantly contain the pandemic by reducing viral transmission. This article focuses on the development and mechanism of action of the vaccines, their safety and efficacy profile as well as indications for vaccination and current recommendations for the use of vaccines in special groups of people, such as convalescent, immunosuppressed and pregnant patients. Finally, currently open scientific questions are addressed.

Bridging antifungal prophylaxis with 50 mg or 100 mg micafungin in allogeneic stem cell transplantation: A retrospective analysis.

OBJECTIVE: Fluconazole or posaconazole is a standard of care in antifungal prophylaxis for patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). However, many patients need to interrupt standard prophylaxis due to intolerability, drug-drug interactions, or toxicity. Micafungin has come to prominence for these patients. However, the optimal biological dose of micafungin stays unclear. METHODS: We retrospectively evaluated the efficacy of micafungin as antifungal prophylaxis in HSCT patients. Micafungin was applied as bridging in patients who were not eligible to receive oral posaconazole. Micafungin was either given at a dose of 100 mg or 50 mg SID. RESULTS: A total of 173 patients received micafungin prophylaxis, 62 in the 100 mg and 111 in the 50 mg dose group. The incidence of probable or proven breakthrough IFDs during the observation period was one in the 100 mg and one in the 50 mg group. Fungal-free survival after 100 days was 98% and 99% (P = .842), and overall survival after 365 days was 60% and 63% (P = .8) respectively. In both groups, micafungin was well tolerated with no grade 3 or 4 toxicities. CONCLUSION: In this retrospective analysis, which was not powered to detect non-inferiority, micafungin is effective and complements posaconazole as fungal prophylaxis in HSCT.

Attributable mortality of candidemia after introduction of echinocandins.

OBJECTIVES: Candidemia is among the most frequent nosocomial bloodstream infections. Landmark case-control studies on amphotericin B and fluconazole estimated attributable mortality rates of 38% and 49%, respectively. After introduction of echinocandins, these may have decreased. METHODS: In a case-control design, 100 consecutive, hospitalised patients with candidemia were enrolled at the University Hospital of Cologne, Germany between 2014 and 2017. Controls were patients without candidemia matched for age, sex, year and duration of hospitalisation, main admission diagnosis and Patient Clinical Complexity Level (PCCL). Main data captured were risk factors for candidemia, attributable mortality rates and diagnostic and therapeutic adherence according to the EQUAL Candida score. RESULTS: Overall mortality rates for cases and controls were 43% and 17% (P < .001), respectively; day 30 mortality rates were 38% and 11% (P = .03), accounting for an attributable mortality of 26% and 27%. Guideline adherence was higher in surviving vs non-surviving patients: while survivors reached a median of 17 (IQR: 16-19) points, non-surviving cases reached a median 16 (IQR: 14-18) points out of 22 maximum achievable points (P = .028). Risk factors for candidemia were more frequent in cases compared to control patients, especially chronic pulmonary disease (25% vs 16%; P = n.s.), chronic liver disease (21% vs 6%; P = .002), stay on intensive care unit (70% vs 64%; P = n.s.), respiratory failure (56% vs 50%; P = n.s.) and central venous catheter (97% vs 35%; P < .001). CONCLUSIONS: Attributable mortality of nosocomial candidemia is still substantial but has decreased compared to previous studies with similar design.

Quantifying guideline adherence in mucormycosis management using the EQUAL score.

OBJECTIVES: Mucormycosis is a difficult-to-diagnose life-threatening disease with high morbidity and mortality. Adherence to guidelines that lead through complex management and support clinical decisions is however rarely reported. By applying the EQUAL Score, our study evaluates the management of mucormycosis at the University Hospital of Cologne, Germany. METHODS: We performed a retrospective chart review of patients with mucormycosis at the University Hospital of Cologne. Data collection comprised items for quality assessment in mucormycosis management according to the EQUAL Mucormycosis Score and economics. RESULTS: Of 29 patients identified, 27 were documented retrospectively. Eight patients of 18 with neutropenia (>10 days) or receiving allogeneic stem cell transplantation (44.4%) received mould active prophylaxis. Chest CT was done in 21 patients (77.8%), while BAL and direct microscopy of BAL fluid was performed in 22 patients (81.5%), culture in 22 (81.5%) and fungal PCR in 24 (88.9%). First-line treatment was liposomal amphotericin B in 19 patients (70.4%). Isavuconazole or posaconazole with therapeutic drug monitoring was used in four (14.8%) and in one patient (3.7%), respectively. In our cohort, crude mortality was 51.9% (n = 14) with a median survival time of 113 days. During the management of the 27 patients, 450 points (53.8%) of the maximum EQUAL Mucormycosis Score were achieved (median 15 points, range 6-30). CONCLUSIONS: We observed management of mucormycosis aligning with current guidelines and hope to encourage other groups to use the EQUAL Score in routine clinical settings. Future studies will evaluate whether guideline adherence in mucormycosis management improves patient outcome.

Risk factors and mortality in invasive Rasamsonia spp. infection: Analysis of cases in the FungiScope® registry and from the literature.

BACKGROUND: The new Rasamsonia spp. complex can develop invasive infection in immunosuppression or chronic pulmonary disease. It has potential to be misidentified as other genera due to morphological similarities. Nowadays, there is a gap of knowledge on this fungi. OBJECTIVES: To provide knowledge base of risk factors and therapeutic decisions in invasive Rasamsonia spp. complex infection. PATIENTS/METHODS: Cases of invasive infection due to Rasamsonia spp. (formerly Geosmithia/Penicillium spp.) from FungiScope® registry and all reported cases from a literature were included. RESULTS: We identified 23 invasive infections due to Rasamsonia spp., six (26.1%) in the FungiScope® registry. Main risk factors were chronic granulomatous disease (n = 12, 52.2%), immunosuppressive treatment (n = 10, 43.5%), haematopoietic stem cell transplantation (n = 7, 30.4%), graft-versus-host disease and major surgery (n = 4, 17.4%, each). Predominantly affected organs were the lungs (n = 21, 91.3%), disease disseminated in seven cases (30.4%). Fungal misidentification occurred in 47.8% (n = 11), and sequencing was used in 69.6% of the patients (n = 16) to diagnose. Breakthrough infection occurred in 13 patients (56.5%). All patients received antifungal treatment, mostly posaconazole (n = 11), caspofungin (n = 10) or voriconazole (n = 9). Combination therapy was administered in 13 patients (56.5%). Susceptibility testing showed high minimum inhibitory concentrations for azoles and amphotericin B, but not for echinocandins. No preferable treatment influencing favourable outcome was identified. Overall mortality was 39% (n = 9). CONCLUSION: Rasamsonia spp. are emerging fungi causing life-threatening infections, especially in immunocompromised and critically ill patients. Mortality is high. Treatment is challenging and clinicians dealing with this patient population should become aware of this infection constituting a medical emergency.

Candida auris in Germany and Previous Exposure to Foreign Healthcare.

The emerging yeast Candida auris has disseminated worldwide. We report on 7 cases identified in Germany during 2015-2017. In 6 of these cases, C. auris was isolated from patients previously hospitalized abroad. Whole-genome sequencing and epidemiologic analyses revealed that all patients in Germany were infected with different strains.

Surgical site infections: current management and role of new antibiotics.

PURPOSE OF REVIEW: Management of SSI comprises prevention, extensive diagnosis, and appropriate treatment as well as follow-up. All these are interrelated matters. This review gives a brief update on the latest developments in the field, specifically on new antibiotics that may find a place in this complex field. RECENT FINDINGS: Avibactam and dalbavancin are novel antiinfectives. Although randomized controlled trials in SSI are lacking to date, preliminary data show that new drugs may be alternatives to existing treatment. Currently, they should be used only on the ground of susceptibility testing, and if standard drugs are inappropriate. SUMMARY: Correct diagnosis of SSI depends on the type of procedure performed. However, early detection is of great importance for proper management across all surgical interventions. The management of SSI includes consistent antibiotic therapy, wound drainage, and rigorous wound debridement as appropriate. Specific wound management thereafter depends on the location and nature of infection. If available, culture findings guide changes in antibiotic therapy. Avibactam and dalbavancin are novel antiinfectives that should be used on ground of susceptibility testing in the absence of appropriate alternatives. Follow-up is particularly important in patients with prosthesis in place. The most promising approach of postdischarge surveillance is a matter of ongoing debate.

Development and validation of the European QUALity (EQUAL) score for mucormycosis management in haematology.

BACKGROUND: Mucormycosis is a life-threatening infection in immunocompromised patients and in haematological malignancy patients in particular. OBJECTIVES: Our aim was to develop and evaluate a scoring tool to measure adherence to current guidelines for mucormycosis. METHODS: Current guidelines of scientific societies on mucormycosis management were reviewed. We assembled diagnostic, treatment and follow-up milestones and designed the EQUAL Mucormycosis Score. The EQUAL Mucormycosis Score was evaluated in the ECMM Excellence Centres. RESULTS: An 18-item tool with one to three points per item resulted in a maximum achievable score depending on disease complexity and ranging from 25 to 32 points. Given variable patient disease course, the diagnostic score is higher in patients with positive fungal culture and biopsy, thus reflecting more decision points and higher management complexity. Eleven patients from two centres were included during the study period. A total of 200 EQUAL Mucormycosis Score points were achieved, which is 62.7% of the maximum EQUAL Mucormycosis Score of 319 points achievable in that cohort (median 18 points, range 7-27). The total score accomplished for diagnostic procedures was 112 of 165 points (67.9%), for first-line treatment 54 of 88 (61.4%) and for follow-up management 34 of 66 points (51.5%). CONCLUSIONS: The EQUAL Mucormycosis Score quantitates adherence to current guideline recommendations for mucormycosis management. With 62.7% of maximum achievable score points, a first result is obtained that may serve as a reference for future evaluations. It remains to be shown whether guideline adherence and mortality rates correlate.

Matched-paired analysis of patients treated for invasive mucormycosis: standard treatment versus posaconazole new formulations (MoveOn).

BACKGROUND: First-line antifungal treatment for invasive mucormycosis (IM) consists of liposomal amphotericin B. Salvage treatment options are limited and often based on posaconazole oral suspension. With the approval of posaconazole new formulations, patients could benefit from improved pharmacokinetics, safety and tolerability. OBJECTIVES: Our aim was to assess the effectiveness of posaconazole new formulations for IM treatment. METHODS: We performed a case-matched analysis with proven or probable IM patients from the FungiScope® Registry. First-line posaconazole new formulations (1st-POSnew) and first-line amphotericin B plus posaconazole new formulations (1st-AMB+POSnew) cases were matched with first-line amphotericin B-based (1st-AMB) treatment controls. Salvage posaconazole new formulations (SAL-POSnew) cases were matched with salvage posaconazole oral suspension (SAL-POSsusp) controls. Each case was matched with up to three controls (based on severity, haematological/oncological malignancy, surgery and/or renal dysfunction). RESULTS: Five patients receiving 1st-POSnew, 18 receiving 1st-AMB+POSnew and 22 receiving SAL-POSnew were identified. By day 42, a favourable response was reported for 80.0% (n = 4/5) of patients receiving 1st-POSnew, for 27.8% (n = 5/18) receiving 1st-AMB+POSnew and for 50.0% (n = 11/22) receiving SAL-POSnew. Day 42 all-cause mortality of patients receiving posaconazole new formulations was lower compared with controls [20.0% (n = 1/5) in 1st-POSnew versus 53.3% (n = 8/15) in 1st-AMB; 33.3% (n = 6/18) in 1st-AMB+POSnew versus 52.0% (n = 26/50) in 1st-AMB; and 0.0% (n = 0/22) in SAL-POSnew versus 4.4% (n = 2/45) in SAL-POSsusp]. CONCLUSIONS: Posaconazole new formulations were effective in terms of treatment response and associated mortality of IM. While posaconazole new formulations may be an alternative for treatment of IM, the limited sample size of our study calls for a cautious interpretation of these observations.

A novel approach to candidemia? The potential role of checkpoint inhibition.

Infections with Candida spp. cause significant morbidity and mortality despite intensive treatment with antifungal agents. Novel treatment options are urgently needed. Predominately immunocompromised patients are affected. This warrants the conclusion that strengthening host immunity may have the potential to improve outcome. Recent studies imply a potential benefit of checkpoint inhibition reversing hyporesponsiveness of innate and adaptive immunity during invasive fungal infections and invasive candidiasis in particular. We here give a brief overview of first preclinical data in vitro and in vivo and clinical evidence in selected cases.