Ceftazidime/Avibactam and Ceftolozane/Tazobactam for Multidrug-Resistant Gram Negatives in Patients with Hematological Malignancies: Current Experiences

Abstract

Patients suffering from hematological malignancies are at high risk for severe infections, including in particular bloodstream infections, which represent one of the most frequent life-threatening complications for these patients, with reported mortality rates reaching 40%. Furthermore, a worrisome increase in antimicrobial resistance of Gram-negative bacteria (e.g., cephalosporin- and/or carbapenem-resistant Enterobacteriaceae and multidrug-resistant (MDR) Pseudomonas aeruginosa) involved in severe infectious complications among patients with hematological malignancies has been reported during the last years. The two novel combination of cephalosporins and β-lactamase inhibitors, ceftolozane/tazobactam and ceftazidime/avibactam, were recently approved for treatment of complicated intra-abdominal and urinary tract infections and nosocomial pneumonia and display activity against several MDR Gram-negative strains. Although not specifically approved for neutropenic and/or cancer patients, these drugs are used in this setting due to increasing rates of infections caused by MDR Gram-negative bacteria. The aim of this review is to describe the actual evidence from scientific literature about the “real-life” use of these two novel drugs in patients with hematological malignancies and infections caused by MDR Gram-negative bacteria.

Ceftazidime-Avibactam for the Treatment of Serious Gram-Negative Infections with Limited Treatment Options: A Systematic Literature Review

“…Similarly, Dietl et al (2020) reviewed 11 observational and comparative studies of ceftazidime-avibactam in patients with CPE infections (including 8 in patients with KPC-and 3 in patients with OXA-48-producing Enterobacterales) [94], all of which were also included in the current review [18,19,23,28,30,31,34,38,41,49,56]. Finally, a systematic review of severe infectious complications among patients with haematological malignancies identified three studies of ceftazidime-avibactam [95], of which two were included in the current review (the third was excluded as it involved treatment of an infection caused by an MBL-producing organism) [23,53].…”

Successful Engraftment of HLA-matched Peripheral Hematopoietic-stem-cell Transplantation for Severe Aplastic Anemia With Multidrug-resistant Bacterial and Fungal Infections

“…Infections caused by various MDR bacteria increase the risk of death signi cantly. Ceftazidimeavibactam (CAZ-AVI) is a novel synthetic β-lactamase inhibitor combination for a range of MDR Gramnegative infection [15,16], which was approved by the FDA in 2017. CAZ-AVI has been successfully used in patients with limited treatment options for complicated intra-abdominal infections and hospitalacquired, ventilator-associated pneumonia caused by CRE and other multidrug Gram-negative bacteria [17][18][19].…”

Carbapenem-Resistant Enterobacteriaceae—Implications for Treating Acute Leukemias, a Subgroup of Hematological Malignancies

“…There is a lack of RCTs focusing specifically on treating infections caused by CR GNB with ceftazidime/avibactam. Experience from studies comparing treatment with ceftazidime/avibactam to other regimens in the treatment of severe infections caused by CRE has been associated with higher rates of clinical success and survival [ 122 , 123 , 124 ]. A point of specific interest is the broad inhibitory profile of avibactam (inhibits class A, B, and D β-lactamases ( Table 2 ), including many of the most common carbapenemases in these classes).…”