Background: Carbapenem-resistant Gram-negative bacteria are recognized as a cause of difficult-to-treat infections associated with high mortality.Objectives: To perform a systematic review of currently available data on distribution, characteristics and outcome associated with carbapenem-resistant bloodstream infections in adult neutropenic patients.Methods: Included studies were identified through Medline, Embase and Cochrane databases between January 1995 and April 2016. Random effect meta-analysis was used to quantify the association between carbapenem resistance and mortality and between carbapenem exposure and resistance.Results: A total of 30 studies from 21 countries were included. Overall carbapenem resistance varied from 2% to 53% (median 9%) among studies. Infections due to carbapenem-resistant Pseudomonas spp. were reported in 18 (60%) studies showing high median resistance rates (44% of all carbapenem-resistant Gram-negatives and 19% of Pseudomonas isolates). Resistance of Enterobacteriaceae was less commonly reported and bloodstream infections due to carbapenem-resistant Klebsiella spp. were mainly documented from endemic areas (Greece, Italy, Israel). Carbapenem resistance in Acinetobacter spp. was reported in 9 (30%) studies (median resistance 58% of Acinetobacter isolates). Mortality rates ranged from 33% to 71% (median 50%) in patients with carbapenem-resistant infections. Carbapenem resistance appeared to correlate with mortality (OR 4.89,) and previous exposure to carbapenems (OR 4.63,.Conclusions: Carbapenem resistance represents a threat to neutropenic patients. In this group, resistance is likely promoted by previous carbapenem use and leads to high mortality rates. The knowledge of resistance patterns is crucial and can direct clinicians in the use of alternatives to carbapenem-based regimens.

bla NDM is a major mechanism of resistance of Gram-negative bacteria to β-lactam antibiotics including the carbapenems. bla NDM has been acquired by a large range of Gram-negative bacilli, especially by the Enterobacteriaceae and Acinetobacter spp. The combination of human factors (suboptimal antibiotic stewardship and infection control, movement of people between countries) plus bacterial factors (hospital adapted clones, environmental persistence and prolific horizontal gene transfer) have led to global spread of bla NDM at a rapid pace. Treatment options for New Delhi metallo-β-lactamase (NDM) producers are very limited. For serious infections, combination therapy including a polymyxin is preferred. However, resistance to polymyxins is emerging. Clearly, substantial international efforts must be made to control the spread of NDM producers or else many of the advances of modern medicine may be undermined by untreatable infections.

e bla NDM has been reported in different Enterobacteriaceae species and on numerous plasmid replicon types (Inc). Plasmid replicon typing, in combination with genomic characteristics of the bacterial host (e.g., sequence typing), is used to infer the spread of antimicrobial resistance determinants between genetically unrelated bacterial hosts. The genetic context of bla NDM is heterogeneous. In this study, we genomically characterized 12 NDM-producing Enterobacteriaceae isolated in Australia between 2012 and 2014: Escherichia coli (n ‫؍‬ 6), Klebsiella pneumoniae (n ‫؍‬ 3), Enterobacter cloacae (n ‫؍‬ 2) and Providencia rettgeri (n ‫؍‬ 1). We describe their bla NDM genetic contexts within Tn125, providing insights into the acquisition of bla NDM into Enterobacteriaceae. IncFII-type (n ‫؍‬ 7) and IncX3 (n ‫؍‬ 4) plasmids were the most common plasmid types found. The IncHI1B (n ‫؍‬ 1) plasmid was also identified. Five different bla NDM genetic contexts were identified, indicating four particular plasmids with specific bla NDM genetic contexts (NGCs), three of which were IncFII plasmids (FII-A to -C). Of note, the bla NDM genetic context of P. rettgeri was not conjugative. Epidemiological links between our NDM-producing Enterobacteriaceae were established by their acquisition of these five particular plasmid types. The combination of different molecular and genetic characterization methods allowed us to provide insight into the spread of plasmids transmitting bla NDM .

In a prospective collection of 3GC-R E. coli causing BSI, community-associated Clade C1/C2 ST131 predominate in association with blaCTX-M ESBLs, although a significant proportion of non-ST131 strains carried blaCMY-2.