Epidemiology of Invasive Fungal Diseases in Patients with Hematologic Malignancies and Hematopoietic Cell Transplantation Recipients Managed with an Antifungal Diagnostic Driven Approach

Patients with hematologic malignancies and hematopoietic cell transplant recipients (HCT) are at high risk for invasive fungal disease (IFD). The practice of antifungal prophylaxis with mold-active azoles has been challenged recently because of drug–drug interactions with novel targeted therapies. This is a retrospective, single-center cohort study of consecutive cases of proven or probable IFD, diagnosed between 2009 and 2019, in adult hematologic patients and HCT recipients managed with fluconazole prophylaxis and an antifungal diagnostic-driven approach for mold infection. During the study period, 94 cases of IFD occurred among 664 hematologic patients and 316 HCT recipients. The frequency among patients with allogeneic HCT, autologous HCT, acute leukemia and other hematologic malignancies was 8.9%, 1.6%, 17.3%, and 6.4%, respectively. Aspergillosis was the leading IFD (53.2%), followed by fusariosis (18.1%), candidiasis (10.6%), and cryptococcosis (8.5%). The overall 6-week mortality rate was 37.2%, and varied according to the host and the etiology of IFD, from 28% in aspergillosis to 52.9% in fusariosis. Although IFD occurred frequently in our cohort of patients managed with an antifungal diagnostic driven approach, mortality rates were comparable to other studies. In the face of challenges posed by the use of anti-mold prophylaxis, this strategy remains a reasonable alternative.

Epidemiology of visceral mycoses in patients with acute leukemia and myelodysplastic syndrome: Analyzing the national autopsy database in Japan

Visceral mycoses (VM) are a deadly common infection in patients with acute leukemia and myelodysplastic syndrome (MDS). We retrospectively analyzed the data from the centralized “Annual Report of Autopsy Cases in Japan” that archives the national autopsy cases since 1989. Among the total of 175,615 archived autopsy cases, 7183 cases (4.1%) were acute leukemia and MDS patients. While VM was only found in 7756 cases (4.4% in total cases), we found VM had a disproportionally high prevalence among acute leukemia and MDS patients: 1562 VM cases (21.7%) and nearly sixfold higher in prevalence. Aspergillus spp. was the most predominant causative agent (45.0%), and Candida spp. was the second (22.7%) among confirmed single pathogen involved cases. The prevalence of Candida spp. infection decreased about 50% due to the widely use of fluconazole prophylaxis, which may skew toward doubling of the Mucormycetes incidence compared to 30 years ago. Complicated fungal infection (> one pathogen) was 11.0% in acute leukemia and MDS in 2015. It was 14.7 times higher than in other populations. Among 937 patients who received allogeneic hematopoietic cell transplantation (HCT), the prevalence of VM was 28.3% and 23.3% with GVHD. Aspergillus spp. was less prevalent, but Candida spp. was more associated with GVHD. Its prevalence remains stable. Although Aspergillus spp. was the primary causative agent, non-albicans Candida spp. was increasing as a breakthrough infection especially in GVHD cases. Complicated pathogen cases were more common in acute leukemia and MDS.

Fluconazole Prophylaxis of Candida Infections in Preterm Neonates

Infections belong to the most serious health problems in neonates. Invasive candidiases are one of the leading causes of mortality and morbidity in Neonatal intensive care units (NICUs). A more cautious approach is adequate when dealing with fungal infections in premature neonates. Sometimes it is necessary to cure an infection at the very beginning just before manifestation of clinical symptoms. Neonatal colonization due to Candida albicans or non-albicans Candidae predisposes to invasive candidiasis. Pregnancies complicated by preterm delivery should be considered for screening and treatment of maternal Candida colonization to decrease the occurrence of neonatal fungal colonization and its consequences. It is important to prevent infection to spread among patients and avoid complications. Prophylaxis in neonates must be safe and effective. Most authors prefer selective prophylaxis. Fluconazole is the drug of choice for prophylaxis in extremely low birth weight (ELBW) neonates. The prophylaxis is beneficial especially in NICUs with high rates of invasive candidiases. The authors describe benefits and trends in prophylaxis. They also summarize evidence on timing, dosing, and effect of fluconazole prophylaxis.

Fungal Ecology in a Tertiary Neonatal Intensive Care Unit after 16 Years of Routine Fluconazole Prophylaxis: No Emergence of Native Fluconazole-Resistant Strains

Objective We analyzed the fungal ecology of a neonatal intensive care unit (NICU) over a period of 20 consecutive years following the introduction of routine fluconazole prophylaxis for all very low birth weight (VLBW; <1,500 g at birth) preterm babies. The aim was to detect the possible appearance of any ecological shifts toward the emergence of native fluconazole-resistant (NFR) fungal species. Study Design This was a retrospective analysis of clinical and microbiological data of VLBW preterm neonates admitted to a large tertiary NICU in Italy from 1997 to 2016 and surviving more than 3 days. Colonization and infection incidence rates, both for fluconazole-sensitive Candida spp and NFR Candida spp, were calculated for each year. We compared the first 4-year period without prophylaxis (1997–2000) with the last 16-year period with use of routine fluconazole prophylaxis (2000–2016). Results Overall, the incidence of fungal colonization significantly decreased after the introduction of prophylaxis (from 43.4% to 16.5%) as well as the systemic fungal infection incidence (from 16% to 3.7%). The proportion of colonization and infection by NFR Candida spp, on the other hand, did not increase, remaining stable throughout the 16 years of exposure to fluconazole. During the prophylaxis period, 42 of 1,172 VLBW neonates were colonized by NFR species (3.6%), and of them 11 developed a systemic infection (0.9%). During the preprophylaxis period, colonization by these particular species affected 11 of 285 VLBW neonates (3.8%), and a systemic infection involved 4 neonates (1.4%). Conclusion Fluconazole prophylaxis is effective in decreasing Candida colonization and systemic infections in preterm neonates in NICU and did not cause emergence or shifts toward NFR Candida spp over a 16-year surveillance period.