-Lactam Resistance in Gram-Negative Bacteria: Global Trends and Clinical Impact

Abstract

Microbial drug resistance is an inescapable consequence of the utilization of antimicrobial agents in a given environment. Nowhere is the importance of resistance more evident than among agents of the beta-lactam family. Trends toward increased resistance can be seen among fastidious gram-negative bacteria like Haemophilus influenzae, where ampicillin resistance varies from 1% to 64% globally. For Escherichia coli, ampicillin resistance has risen to > or = 50% in high-risk populations, and resistance to third-generation cephalosporins is now being seen in certain areas. Inducible beta-lactamases have been responsible for increasing multiple beta-lactam resistance among certain Enterobacteriaceae and Pseudomonas aeruginosa, and this has been associated with increased use of newer cephalosporins. Xanthomonas maltophilia with its two inducible beta-lactamases is becoming an increasingly important nosocomial pathogen, especially in areas of heavy imipenem utilization. Only through the recognition of factors associated with increasing resistance and the mechanisms responsible can strategies be designed for minimizing beta-lactam resistance.

Decreasing antibiotic resistance of Enterobacteriaceae by introducing a new antibiotic combination therapy for neutropenic fever patients

“…These bacteria can produce a cephalosporinase that is able to inactivate most of the cephalosporins. 2,3 The majority of these bacteria are inducible Enterobacteriaceae (Enterobacter spp, Serratia spp, Citrobacter spp, Morganella morganii, Providencia spp, Proteus vulgaris, Pantoea agglomerans). The relationship between the emergence of resistance of group I ␤-lactamase-producing organisms and the prior use of extended-spectrum cephalosporins is now clearly proven.…”

Prevalence of Extended-spectrum β-Lactamase and Quinolone Resistance Genes in Escherichia coli Clinical Isolates and their Antibiotic Resistance

“…Expanded-spectrum cephalosporin의 광범위한 사용에 의 해 이들 항생제에 내성을 지닌 Klebsiella pneumonia가 출현하 였으며 [9,24,27], 이 후 Escherichia coli와 다른 소수의 그람음 성 세균에서도 내성이 나타나게 되었다 [26].…”

Opinion of the Scientific Panel on Genetically Modified Organisms on the use of antibiotic resistance genes as marker genes in genetically modified plants

“…Catalytic activity and substrate specificity -The amp r gene encodes TEM-1 β-lactamase (Sanders and Sanders, 1992) which hydrolyses the amide bond in the beta-lactam ring of the antibiotic ampicillin. Substrates for the β-lactamase are ampicillin, penicillin G and amoxycillin.…”

“…The TEM-1 enzyme has only a minor activity against recent cephalosporines and can be inhibited by β-lactamase inhibitors such as clavulanic acid or tazobactam. However, in the case of E. coli, a high expression rate of the β-lactamase may render the bacteria resistant to amoxicillin/tazobactam and other combinations of β-lactams with β-lactamase inhibitors (Sanders and Sanders, 1992). Moreover, mutations in the β-lactamase (e. g. TEM-30 to TEM-41) may result in reduced clavulanic-acid inhibition.…”