Use of carbapenems and glycopeptides increases risk for Clostridioides difficile infections in acute myeloid leukemia patients undergoing intensive induction chemotherapy.

Patients with acute myeloid leukemia (AML) are often exposed to broad-spectrum antibiotics and thus at high risk of Clostridioides difficile infections (CDI). As bacterial infections are a common cause for treatment-related mortality in these patients, we conducted a retrospective study to analyze the incidence of CDI and to evaluate risk factors for CDI in a large uniformly treated AML cohort. A total of 415 AML patients undergoing intensive induction chemotherapy between 2007 and 2019 were included in this retrospective analysis. Patients presenting with diarrhea and positive stool testing for toxin-producing Clostridioides difficile were defined to have CDI. CDI was diagnosed in 37 (8.9%) of 415 AML patients with decreasing CDI rates between 2013 and 2019 versus 2007 to 2012. Days with fever, exposition to carbapenems, and glycopeptides were significantly associated with CDI in AML patients. Clinical endpoints such as length of hospital stay, admission to ICU, response rates, and survival were not adversely affected. We identified febrile episodes and exposition to carbapenems and glycopeptides as risk factors for CDI in AML patients undergoing induction chemotherapy, thereby highlighting the importance of interdisciplinary antibiotic stewardship programs guiding treatment strategies in AML patients with infectious complications to carefully balance risks and benefits of anti-infective agents.

Mould-reactive T cells for the diagnosis of invasive mould infection-A prospective study.

Invasive mould infections (IMI) in immunocompromised patients are difficult to diagnose. Early and targeted treatment is paramount, but minimally invasive tests reliably identifying pathogens are lacking. We previously showed that monitoring pathogen-specific CD4+T cells in peripheral blood using upregulation of induced CD154 positive lymphocytes can be used to diagnose acute IMI. Here, we validate our findings in an independent patient cohort. We stimulated peripheral blood cells from at-risk patients with Aspergillus spp. and Mucorales lysates and quantitated mould-reactive CD4/CD69/CD154 positive lymphocytes via flow cytometry. Mould-reactive lymphocytes were quantitated in 115 at-risk patients. In 38 (33%) patients, the test was not evaluable, mainly due to low T cell counts or non-reactive positive control. Test results were evaluable in 77 (67%) patients. Of these, four patients (5%) had proven IMI and elevated mould-reactive T cell signals. Of 73 (95%) patients without proven IMI, 59 (81%) had mould-reactive T cell signals within normal range. Fourteen (19%) patients without confirmed IMI showed elevated T cell signals and 11 of those received antifungal treatment. The mould-reactive lymphocyte assay identified presence of IMI with a sensitivity of 100% and specificity of 81%. The mould-reactive lymphocyte assay correctly identified all patients with proven IMI. Assay applicability is limited by low T cell counts during bone marrow suppression. The assay has the potential to support diagnosis of invasive mould infection to facilitate tailored treatment even when biopsies are contraindicated or cultures remain negative.

Clostridium difficile infection in patients with acute myelogenous leukemia and in patients undergoing allogeneic stem cell transplantation: epidemiology and risk factor analysis.

Patients receiving treatment for acute myelogenous leukemia (AML) and recipients of allogeneic stem cell transplantation (aSCT) are at high risk of contracting Clostridium difficile infection (CDI), the most frequently observed nosocomial diarrhea and enterocolitis. Data were retrieved from the prospective Cologne Cohort of Neutropenic Patients. Patients hospitalized for aSCT as well as patients receiving treatment for AML were included in the analysis. Risk factor analysis for the occurrence of CDI was performed by backward-stepwise logistic regression (P < .1). During the period from January 2007 to August 2010, 310 hospitalizations of 152 patients with AML and 229 hospitalizations of 223 patients undergoing aSCT were eligible for analysis. Incidence rates for CDI per 10,000 patient days were 17.9 for AML patients and 27.4 for aSCT recipients. Among AML and aSCT patients, median time from initiation of chemotherapy to CDI was 10 days (range, -8 to 101 days) and 17 days (range, 6 to 79), respectively. Logistic regression identified carbapenem exposure to be associated with development of CDI in AML patients (odds ratio [OR], 2.2) and aSCT recipients (OR, 1.4). In both groups, previous exposure to carbapenems was significantly associated with development of CDI. A follow-up study, assessing the effect of an antibiotic stewardship intervention to decrease the administration of carbapenems in hematological high-risk patients, is warranted.

Mucormycosis treated with posaconazole: review of 96 case reports.

Mucormycosis is an emerging invasive fungal infection, primarily affecting immunocompromised patients. The disease is difficult to diagnose and mortality reaches 40% even if treated adequately. Depending on site of infection and risk factors, surgical debridement in combination with systemically active antifungal drugs are the mainstay treatment strategies. Lipid-based amphotericin B is the treatment of choice for first-line therapy while posaconazole may be a promising alternative. We performed a PubMed search on reports of patients with mucormycosis treated with posaconazole. From 2003 to 2011, 96 cases have been published. Diagnosis was based on histology alone in 2 (2.1%) and microbiological evidence in 67 (69.8%), while no data on the diagnostic approach was reported in 27 (28.1%) patients. The most frequent pathogens were Rhizopus spp. (31.2%), followed by Mucor spp. (14.6%). The site of infection was predominantly rhino-orbital (38.5%, of which 43% also had central nervous system [CNS] involvement), followed by disseminated disease (22.1%). A complete response was achieved in 62 (64.6%), partial response in 7 (7.3%) patients, and stable disease in 1 (1%). Overall mortality was 24% (lacking data for three patients). In published case reports on posaconazole treatment for mucormycosis, the drug was frequently and successfully used in combination or as second line therapy.