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Report from the 24th Infectious Diseases Working Party Educational Course - 24-26 November 2021 - Virtual

Infectious Diseases Working Party (IDWP)

Summary report by:

Meir Cherniak and Danna Dror (Session I & II) - Clinical Microbiology and Infectious Diseases, Faculty of Medicine, Hebrew University of Jerusalem; Hadassah Medical Center, Jerusalem, Israel.

Alessio Mesini (Session III)

Maria Stamouli (Session VI & VII) - Director at the 2nd Department of Internal Medicine Propaedeutic, Division of Haematology, Attikon University Hospital, Athens, Greece.

Session I: Spotlight on Fungal infections

Chaired by Johan Maertens (Leuven, Belgium) and Monica Slavin (Melburn, Australia). 

Patricia Manoz (Madrid, Spain) reviewed invasive candidiasis (IC), an uncommon but life threating condition. The IC rates differ between centers and countries. Central line management, antifungals resistance and other questions represent everyday challenges. Current diagnostic and treatment guidelines were reviewed. Several novel therapies widening the treatment options for IC are currently under investigation.  

Rafael de la Camara (Madrid, Spain) presented the complex scenario of invasive aspergillosis (IA) epidemiology, diagnosis, and treatment. IA is mainly diagnosed based on biomarkers or histological investigation. Voriconazole is currently the treatment of choice but the resistance must be considered in certain geographic areas. The current diagnostic approach and management principles were discussed along with review of the recent ECIL guidelines.

Livio Pagano (Rome, Italy) reviewed presentation, diagnosis, and treatment of mucormycosis, a condition leading to the devastating consequences in neutropenic patients. Early diagnosis and multi-displinary management, including pharmacological and surgical approach, can be lifesaving. Diagnosis is based on histological examination of infected tissue. Current overview discussed diagnostic tools and treatment strategies based on recent guidelines. 

Dionysios Neofytos (Geneve, Switzerland) presented the topic of rare fungal infections. Fusarium, Cryptococcus, Histoplasmosis, and other rare fungi can cause severe infections in neutropenic patients. The spectrum of presentation is broad, and the diagnosis can be challenging. Specific findings, such as skin rash in patients with fusariosis, can raise clinical suspicion. The diagnostic approach and specific treatment options were discussed.

Session II: Prophylaxis of infections following HSCT 

Chaired by Dina Averbuch (Jerusalem, Israel) and Malgorzata Mikulska (Genova, Italy). 

Catherine Cordonnier (Creteil, France) presented the current approach to antifungal prophylaxis (AFP). AFP was demonstrated to reduce the risk of invasive fungal infections after HSCT. This presentation discussed the risk factors and the timing of fungal infections following HSCT. Different guidelines-recommended prophylactic regimens were reviewed.

Ronen Ben-Ami (Tel Aviv, Israel) discussed the topic of breakthrough invasive fungal infections (BIFI). BIFI were reported on any antifungals, regardless of their spectrum of activity. Risk factors to BIFI development and the spectrum of pathogens were discussed. The overview presented the differential diagnosis of BIFI, the complex diagnostic process and management strategy.

Per Ljungman (Stockholm, Sweden) presented the current management of CMV in the era of letermovir prophylaxis. Letermovir is a potent and a safe drug with a specific activity against CMV.  Benefits of CMV prophylaxis in different HSCT populations, reduction of CMV infection and disease, and influence on mortality were discussed.

Dafna Yahav (Tel Aviv, Israel) reviewed benefits and risks of fluoroquinolone prophylaxis (FQP). Past literature demonstrated reduced mortality and bacteremia rates in neutropenic patients on FQP. Growing FQ resistance undermines prophylaxis efficacy. FQP disadvantages include increased risk of multidrug resistant Gram-negative bacteremia, and side effects.

Session III: Diagnosis and treatment of infections

Chaired by Andreas Groll (Münster, Germany) and Jan Styczynski (Bydgoszcz, Poland).

Jacob Moran-Gilad (Jerusalem, Israel) presented new procedures both dependent and independent from bacteria culture will allow to reduce diagnostics time, such as metagenomics or WGS and thanks to which the entire pathogen’s genome can be interrogated. These tools have a promising role in identifying hospital outbreaks resistance mechanisms.

Dina Averbuch (Jerusalem, Israel) presented an overview of novel carbapenem-resistant Gram negative active molecules. Real-life data for these antibiotics are supportive but limited in the immunocompromised patient or in the treatment of bacteremia. Furthermore, despite the recent use of these molecules, resistant strains have already been reported.

The combination with other drugs isn’t routinely recommended and should be limited to certain situation. The role of these new antibiotics as empirical treatment of febrile neutropenia has yet to be defined.

Evaluation of PK/PD parameters role in the success of an antibiotic therapy was highlighted by Pier Giorgio Cojutti (Bologna, Italy). Prolonged infusions and/or increased doses increase the efficacy of beta-lactams, ensuring concentrations above MIC, and may reduce resistances selection. TDM is fundamental during voriconazole treatment for CNS aspergillosis, and it can be applied to new azoles too.

Elio Castagnola (Genova, Italy) showed the differences between adult and pediatric undergoing HSCT. They could be found in clinical presentation of infections, epidemiology, laboratory or radiological diagnostics, and ultimately in treatment. Pediatric field is burdened by a limited scientific evidence and clinical practice is often borrowed from the adult patient experiences.

Session VI: The classic and the new

Chaired by Per Ljungman

Simone Cesaro (Verona, Italy) gave a review on the management of Adenovirus (HAdV), a virus that, in the HSCT setting, can cause life-threatening disseminated disease especially in the pediatric population. Risk factors, incidence and outcome were presented. HAdV-DNAemia monitoring is recommended in high-risk patients and at least upon clinical suspicion in other risk categories so that pre-emptive treatment can be promptly initiated. Treatment options include cidofovir, brincidofovir and adoptive immunotherapy as well as reduction of immunosuppression.

Jan Styczynski (Bydgoszcz, Poland) focused on viruses causing encephalitis. HHV6 infection (clinical symptoms, diagnostics, risk factors) was analyzed. PTCy may lead to a higher rate of HHV6 reactivation and disease. Treatment is based on ganciclovir, foscarnet and reduction of immunosuppression. HHV6 encephalitis has also been reported following CAR-T-cell therapy. JCV can cause progressive multifocal encephalopathy with a high mortality rate and no specific treatment currently available. Pembrolizumab and notably CTL therapy have potential as valuable treatments.

Dan Engelhard (Jerusalem, Israel) discussed the management of HSV and VZV. Clinical manifestations and risk factors were revisited, as emerging resistance to val/acyclovir has been reported for both HSV and VZV infections. Pritelivir and amenamevir are helicase-primase inhibitors that could be used as alternatives to foscarnet and cidofovir for val/acyclovir resistant HSV and VZV. Varicella and Zoster vaccines were also discussed. The new subunit-adjuvanted VZ vaccine can be useful in the HSCT setting (so far data suggest that it is far less immunogenic in allo-SCT compared to auto-SCT).

Session VII: COVID-19

Chaired by Galia Rahav and Simone Cesaro    

Per Ljungman (Stockholm, Sweden) offered an update on COVID-19 and the EBMT registry. Risk factors and outcome in patients, who had undergone Auto/AlloSCT and CAR-T cell therapy, were presented. ECIL-2021 recommendations were discussed: deferral of conditioning should be considered in case of COVID infection. HSCT patients should receive COVID-19 vaccine (preferably at least 6 months after transplant). Earlier vaccination can be considered if there is high prevalence of the virus in the community albeit with a lower likelihood of immune response.

Malgorzata Mikulska (Genova, Italy) discussed the treatment of COVID-19 in hematology patients. She gave an insight into the viral and host/inflammatory phase of COVID-19 and treatments applied in the general population. Remdesivir, molnupiravir have better results in the viral (early) phase, while steroids show clear benefit in the host /inflammatory phase. There is little separate data on immunocompromised patients: possibly there is a prolonged viral phase and prolonged shedding in some.

Sylvain Meylan (Lausanne, Switzerland) focused on monoclonal antibodies (mAbs) for COVID-19. MAbs are well tolerated. Early intervention is important, as they are useful mainly for prophylaxis and mild to moderate disease. Their role in severe disease is limited: greatest benefit from mAbs is observed in seronegative patients with high viral load at baseline, so serοtyping in admission is worth considering. There is limited data in HCST patients, though partial protection can be expected. Long acting antibodies (LAAB) could be useful in pre/post-exposure prophylaxis in these patients.