Data for this Review were obtained from publications identified by systematically searching PubMed, focusing on those published from 2000 to 2008. Search items included “KPC”, “carbapenemases”, and “carbapenem-hydrolyzing β-lactamases”. Articles retrieved were in English. In addition, unpublished data presented at the 47th Interscience Congress on Antimicrobial Agents and Chemotherapy in Chicago (USA, 2007) were referenced.
ReviewThe real threat of Klebsiella pneumoniae carbapenemase-producing bacteria
Section snippets
First detection, structure, and hydrolysis spectrum
The first KPC producing isolate was K pneumoniae from North Carolina, USA, identified in 1996.8 This klebsiella isolate was resistant to all β lactams, but carbapenem minimum inhibitory concentrations (MICs) were slightly decreased after addition of clavulanic acid, a β lactamase inhibitor. The discovery of this plasmid-encoded β lactamase, KPC-1, was followed by several publications of another single aminoacid variant, KPC-2, in hospitalised patients from the east coast of the USA.9, 10, 11
Clinical features and epidemiology
KPC-associated enterobacterial infections do not seem to be specific to sites, organs, or tissues. Most of the infections are either systemic infections, occurring in patients with multiple invasive devices or urinary tract infections without an indwelling catheter, particularly in immunocompromised patients.21, 22
Specific virulence factors associated with KPC-producing bacteria have not been reported. Risk factors associated with the acquisition of KPC-producing bacteria included prolonged
Molecular genetics
Genetic analysis of blaKPC genes indicates that their mobility may be associated with spread of strains, plasmids, and transposons.8, 10, 11, 13, 14, 15, 16, 17, 20, 25, 26, 31, 35, 36, 37, 44, 45, 51, 52, 53, 54, 55, 56, 62 The fact that different bacterial species and different K pneumoniae clones may carry KPC β lactamases is evidence of their ease of transmission.37 The blaKPC genes have usually been identified in large plasmids varying in size and structure. In most cases, the plasmids
Detection
Detection of KPC-producing bacteria based only on susceptibility testing is not easy, due to heterogeneous expression of β-lactam resistance (table). Several KPC-producing bacteria have been reported as susceptible to carbapenems.21, 32 To fully express the carbapenem-resistance trait, a second mechanism, such as an outer-membrane permeability defect, may be required.8, 13, 20, 51 Detection of the level of susceptibility of KPC-producing bacteria remains difficult whatever the technique used:
Treatment options
Options for treating infected patients with KPC-producing Enterobacteriaceae are limited. Although some isolates have been reported to be susceptible to cephamycins and cefepime, with MICs being close to, but below, the breakpoints, it is likely that neither expanded-spectrum cephalosporins nor carbapenems (including newer carbapenems such as doripenem)77 could be indicated for treating systemic infections due to KPC-producing bacteria. Furthermore, it has been shown that, during imipenem and
Conclusions
KPC-producing bacteria have increasingly been isolated worldwide, mostly in the form of K pneumoniae. The spread of KPC-producing K pneumoniae is worrying, from a public health point of view, since this species is prone to be the source of many hospital-acquired infections in severely ill patients, and is well-known for its ability to accumulate and transfer resistance determinants as illustrated with ESBLs. In addition, the recent identification of KPC in E coli infected patients hospitalised
Search strategy and selection criteria
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