Current Epidemiology and Growing Resistance of Gram-Negative Pathogens

Abstract

In the 1980s, Gram-negative pathogens appeared to have been beaten by oxyimino-cephalosporins, carbapenems, and fluoroquinolones. Yet these pathogens have fought back, aided by their membrane organization, which promotes the exclusion and efflux of antibiotics, and by a remarkable propensity to recruit, transfer, and modify the expression of resistance genes, including those for extended-spectrum β-lactamases (ESBLs), carbapenemases, aminoglycoside-blocking 16S rRNA methylases, and even a quinolone-modifying variant of an aminoglycoside-modifying enzyme. Gram-negative isolates -both fermenters and non-fermenters-susceptible only to colistin and, more variably, fosfomycin and tigecycline, are encountered with increasing frequency, including in Korea. Some ESBLs and carbapenemases have become associated with strains that have great epidemic potential, spreading across countries and continents; examples include Escherichia coli sequence type (ST)131 with CTX-M-15 ESBL and Klebsiella pneumoniae ST258 with KPC carbapenemases. Both of these high-risk lineages have reached Korea. In other cases, notably New Delhi Metallo carbapenemase, the relevant gene is carried by promiscuous plasmids that readily transfer among strains and species. Unless antibiotic stewardship is reinforced, microbiological diagnosis accelerated, and antibiotic development reinvigorated, there is a real prospect that the antibiotic revolution of the 20th century will crumble.

Development of a multiplex PCR system and its application in detection of blaSHV, blaTEM, blaCTX-M-1, blaCTX-M-9 and blaOXA-1 group genes in clinical Klebsiella pneumoniae and Escherichia coli strains

“…These results are in agreement with previous reports that have projected CTX-14 to be the most common in different parts of China followed by CTX-M-3. [36][37][38]41 Our data also indicate that the CTX-M-15 enzyme, which has been reported to have a worldwide distribution, especially in E. coli and with a great potential for epidemics, 42 is also available in this region. The four strains of K. pneumoniae possessing ESBL-SHV enzymes (SHV-27 and SHV-33) co-harbored CTX-M-14 with most of the rest carrying SHV-11 and SHV-1.…”

Epidemiology of antimicrobial resistance in bloodstream infections

“…35,51,66 Escherichia coli sequence type (ST)131 with CTX-M-15 ESBL production has a high epidemic potential and spread worldwide. 64,65,67 EARS-Net data indicated that in the EU mean resistance rate to the 3rd generation cephalosporins was 11.9%, ranging 4.4% in Sweden, 38.1% in Bulgaria. 9 The ESBL-positive strains were reported between 71.5% and 100% in different European countries.…”

“…11,110 Several b-lactamases have been described for causing resistance and these include AmpC, ESBL (particularly PER-1) and metallo-b-lactamases. 67 PER-1 producing P. aeruginosa which shows high-level resistance to ceftazidime, but susceptible to clavulanate and tazobactam was widely detected in Turkey and less frequently in several European and Asian countries. 111 Carbapenem resistance in P. aeruginosa is mostly due to porin deficiencies and rarely caused by carbapenemase production.…”

“…66,78 ESBL-encoding plasmids may also encode resistance to aminoglycosides, tetracyclines, sulphonamides and trimethoprim. 67 These plasmids frequently encode an inhibitor-resistant b-lactamase, namely OXA-1 which confers resistance to b-lactamase inhibitors including amoxicillin-clavulanate and piperacillintazobactam. 67,79 Quinolone resistance has been reported 41.8% in US in CR-BSIs and between 11 to 52 percent in invasive isolates from EU countries; 11,17 whereas CAESAR data indicated 8% and 41% resistance among isolates from blood and CSF in Switzerland and Turkey, respectively.…”

“…67 These plasmids frequently encode an inhibitor-resistant b-lactamase, namely OXA-1 which confers resistance to b-lactamase inhibitors including amoxicillin-clavulanate and piperacillintazobactam. 67,79 Quinolone resistance has been reported 41.8% in US in CR-BSIs and between 11 to 52 percent in invasive isolates from EU countries; 11,17 whereas CAESAR data indicated 8% and 41% resistance among isolates from blood and CSF in Switzerland and Turkey, respectively. 10 Aminoglycoside resistance among E. coli and other enteric pathogens is determined by aminoglycosidemodifying enzymes which can be encoded on the same plasmid with ESBLs.…”