This study was made to find the prevalence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae in neonatal intensive care unit (NICU) and to identify the risk factors associated with the acquisition of these organisms. Risk factors associated with ESBL-producing E. coli and/or K. pneumoniae acquisition status of neonates were assessed. Of 253 neonates admitted, 238 entered the active surveillance system. ESBL-producing K. pneumoniae was responsible for 7 infections and 51 colonizations while ESBL-producing E. coli was responsible for 9 infections and 88 colonizations. Concurrent isolation of both the organisms occurred in 30 neonates. The logistic regression model identified 'length of stay in the NICU' as the single independent risk factor. Imipenem, cefepime and amikacin can be suggested as the drugs of choice in our study.
We studied the molecular mechanism of resistance in extended-spectrum b-lactamase (ESBL)-producing Klebsiella pneumoniae isolated from a neonatal intensive care unit (NICU) of one of the hospitals in North India. A total of 3000 clinical samples were collected from a NICU (January 2009 to February 2011), of which 523 strains were K. pneumoniae positive and 262 of them were ESBL-producing K. pneumoniae strains. All of the ESBL-producing clinical isolates were susceptible to carbapenems. However, the majority of the clinical isolates (30-96 %) were resistant to a wide range of antibiotics including antibiotic/inhibitor combinations. The MIC values confirmed that these isolates were highly resistant to cephalosporins and aztreonam. In the 262 ESBL-producing K. pneumoniae isolates, 15 different enterobacterial repetitive intergenic consensus (ERIC)-PCR-typed phylogenetic groups were identified and reconfirmed by PFGE. Characterization of plasmids from each representative member of these phylogenetic groups revealed the presence of three plasmids of different sizes. Conjugation experiments confirmed the presence of different resistance markers only on the 154 kb plasmid. PCR amplification and sequence analysis revealed that bla CTX-M-3 , bla TEM-1 , bla SHV-1 , bla OXA-1 and armA were the predominant resistance markers. Plasmid-replicon typing showed that IncI1-Ic and IncFIA-FIB types are the most prevalent. This study shows the co-existence of multiple ESBL-encoding genes and their polyclonal dissemination among K. pneumoniae clinical isolates in the NICU of a North Indian hospital.
The emergence of antibiotic resistance in bacteria is a serious threat with enormous social and economic implications. The distribution of resistance genes/markers through horizontal gene transfer leads to the dissemination of resistant strains in different parts of the world. The resistant bacteria acquire the ability to overcome resistance by different modes amongst which the expression of β-lactamases is a major factor. The β-lactamase enzymes cleave the amide bond of the β-lactam antibiotics, which constitute about one-third of the antibiotics used all over the world. In a quest to control the spread of resistant bacteria, advanced generations of antibiotics are used either alone or in combination with inhibitors. However, these antibiotics and inhibitors also contain β-lactam ring in their structure and hence are prone to be hydrolyzed by β-lactamase enzymes in the near future. Thus, the severity of the problem is manifested due to the paucity of novel non-β-lactam core containing antibiotics in the drug development stage. One approach to overcome these shortcomings is to use peptide-based inhibitors. Here, we describe the potential use of phage display technique to screen commercially available libraries to pan against β-lactamase enzymes. The main advantage of using peptide-based inhibitors is that the bacteria will not be able to recruit pre-existing defense mechanisms and it will take a long time to evolve a new mechanism in its defense against peptide-based inhibitors.
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