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

Abstract

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.

Third-generation cephalosporin resistant gram-negative bacteraemia in patients with haematological malignancy; an 11-year multi-centre retrospective study

“…First, carbapenems are last-resort antibiotics and using them for all patients with FN—the majority with negative blood cultures and in case of positive blood cultures only a minority is positive with 3GC-R GNB isolates (5.3% of bacteraemia episodes in our study)—could potentially induce or select multidrug-resistant bacteria. Second, the use of carbapenems is associated with the predisposition to fungal infections and development of Clostridium difficile -associated diarrhoea [ 2 , 3 , 29 – 32 ]. Our study illustrates that the value of a surveillance-culture-guided approach, to restrict carbapenems for patients colonized with 3GC-R GNB, is that 76.2% (106/139) of 3GC-R GNB bacteraemia are anticipated by surveillance cultures and would therefore receive appropriate treatment.…”

Third-generation cephalosporin resistant gram-negative bacteraemia in patients with haematological malignancy; the value of a surveillance-culture-guided empirical therapy approach

“…First, carbapenems are last-resort antibiotics and using them for all patients with FN -the majority with negative blood cultures and in case of positive blood cultures only a minority is positive with 3GCR-GNB isolates (5.3% of bacteraemia episodes in our study) -could potentially induce or select multidrug-resistant bacteria. Second, the use of carbapenems is associated with the predisposition to fungal infections and development of Clostridium di cile-associated diarrhoea [2,3,[29][30][31][32]. Our study illustrates that the value of a surveillance-culture-guided approach, to restrict carbapenems for patients colonized with 3GCR-GNB, is that 76.2% (106/139) of 3GCR-GNB bacteraemia are anticipated by surveillance cultures and would therefore receive appropriate treatment.…”

The Dutch Working Party on Antibiotic Policy (SWAB) Recommendations for the Diagnosis and Management of Febrile Neutropenia in Patients with Cancer

“…Its disadvantages, encompassing collateral damage to the (intestinal) microbiome that is caused by the use of unnecessary broad-spectrum antibiotics, is increasingly recognized. In particular, use of carbapenems may be associated with selection of multidrug-resistant bacilli, predisposition to fungal infections, and development of Clostridioides difficile- associated diarrhea [ 53 – 56 ]. However, in addition to reduced prescription of carbapenem antibiotics, antibiotic stewardship depends on proper indication and timely discontinuation of antibiotics.…”