Prevalence of MDR-and XDR Gram-negative pathogens isolated from febrile neutropenic cancer patients with bloodstream infections in Egypt and new synergistic antibiotic combinations

Blood stream infections (BSIs) are defined as positive isolate(s) of blood culture and associated with clinical findings.Cancer patients are among the key candidates for this type of infections due to the methods of treatment they have, such as invasive surgery, chemotherapy, radiotherapy, immunosuppressive agents, or administration of anticancer drugs during hospital stay. Cancer patients sustaining BSI also have higher morbidity and mortality rates. Therefore, speedy identification of isolates, clinical diagnosis, and effective treatment of BSIs decrease the risk of mortality among cancer patients with BSI.Infection with multidrug-resistant (MDR) pathogens including extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae are particularly prevalent among cancer patients.Enterobacteriaceae cause approximately 65%–80% of documented Gram-negative infections in these patients. However, Pseudomonas aeruginosa is also associated with significant morbidity and mortality in immunocompromised hosts.Resistance to the β-lactams is mediated primarily through the production of a variety of β-lactamases including Ambler class C β-lactamases and ESBLs. ESBLs are derived from earlier, plasmid-mediated hydrolyzing enzymes, primarily the TEM and SHV types (both are ESBL enzymes). Other antibiotic resistance coding genes (i.e., to fluoroquinolones [FQs], aminoglycosides, macrolides, carbapenems, etc.) on the same plasmid can confer a MDR phenotype in a subset of these pathogens.Colistin resistance in Gram-negative bacteria (GNB) could be mainly attributed to excessive use of colistin in treating carbapenem-resistant bacteria.Clinical studies strongly suggest that combination therapy is superior to monotherapy for carbapenemase-producing Enterobacte-riacea. To improve potential survival among patients with high risk risk of death, combination therapy is recommended.However, , a combination of two or more active drugs (i.e., colistin, tigecycline, or fosfomycin) with carbapenem is join with a better outcome. A lot antimicrobial guidelines have addressed empirical treatment for such serious infections; however, the rapid treatment of such infections has become a significant problem worldwide. Therefore, in this study, we aimed at evaluating the genetic bases of antimicrobial resistance of MDR GNB in cancer patients against the most commonly used antimicrobial agents used for the treatment of such infections. In extension some antibiotic combinations have been calculate for use against the clinically relevant MDR GNB pathogens recovered in our study.