Prevalence and molecular characterisation of New Delhi metallo-β-lactamases NDM-1, NDM-5, NDM-6 and NDM-7 in multidrug-resistant Enterobacteriaceae from India

Rahman, Mohibur; Shukla, Sanket K.; Prasad, Kashi Nath; Ovejero, Cristina M.; Pati, Binod Kumar; Tripathi, Archana; Singh, Avinash; Srivastava, Ashwini K.; González‐Zorn, Bruno

doi:10.1016/j.ijantimicag.2014.03.003

Cited by 140 publications

(93 citation statements)

References 26 publications

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“…All seven isolates from Afghanistan, including three with rmtF, carried bla NDM in addition to a methylase gene (Table 2). K. pneumoniae producing both RmtF and NDM in isolates with links to India has been previously described (15,16), and our data support the observation that isolates carrying both carbapenemases and 16S methylases are widespread in this region (17)(18)(19). rmtH was found only in isolates from patients treated for injuries sustained during combat operations in Iraq.…”

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confidence: 90%

Detecting 16S rRNA Methyltransferases in Enterobacteriaceae by Use of Arbekacin

et al. 2016

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c 16S rRNA methyltransferases confer resistance to most aminoglycosides, but discriminating their activity from that of aminoglycoside-modifying enzymes (AMEs) is challenging using phenotypic methods. We demonstrate that arbekacin, an aminoglycoside refractory to most AMEs, can rapidly detect 16S methyltransferase activity in Enterobacteriaceae with high specificity using the standard disk susceptibility test. Aminoglycosides play an important role in treating serious infections caused by Gram-positive and -negative organisms, with amikacin, gentamicin, and tobramycin being of particular clinical value (1). In Gram-negative organisms, resistance is primarily mediated by aminoglycoside-modifying enzymes (AMEs), which inactivate the antibiotic through modification of the -OH or -NH 2 groups (2). AMEs are divided into three classes: the ATP (and/or GDP)-dependent aminoglycoside phosphotransferases (APHs), the acetyl-coenzyme A (CoA)-dependent aminoglycoside acetyltransferases (AACs), and the ATP-dependent aminoglycoside nucleotidyltransferases (ANTs) (2). Different classes have different antibiotic substrates, but no single AME confers resistance to all aminoglycosides. In the past decade, transmissible 16S rRNA methyltransferases (16S RMTases) have emerged as a new and worrisome source of aminoglycoside resistance that operates by reducing the affinity of nearly all aminoglycosides for 16S rRNA via ribosomal methylation (3). Since the presence of multiple AMEs can confer resistance to all clinically relevant aminoglycosides, discriminating between AME RMTase activity and 16S RMTase activity using phenotypic methods can be challenging (3).Arbekacin is a semisynthetic aminoglycoside derived from dibekacin (4). It is licensed only in Japan, where it is used to treat septicemia and pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA). However, it also has broad antibacterial activity against Gram-negative bacteria, including strains that are resistant to amikacin, gentamicin, and tobramycin (5). Recently, the U.S. Food and Drug Administration approved arbekacin for use under a protocol at the Walter Reed National Military Medical Center to treat infections for which no other antibiotic is available. Importantly, arbekacin is refractory to nearly all AMEs with the exception of some members of the AAC(6=)-I family and the bifunctional enzyme AAC(6=)/APH(2==) produced by some strains of S. aureus and enterococci (3,4,(6)(7)(8). However, even though these enzymes acetylate arbekacin, the antibiotic still retains some antimicrobial activity (9). We exploited this characteristic to develop a rapid method to detect 16S RMTase activity in Enterobacteriaceae using arbekacin-impregnated susceptibility disks.125 Escherichia coli, 74 Klebsiella pneumoniae, and 22 other Enterobacteriaceae isolates, including Enterobacter (n ϭ 4), Morganella (n ϭ 2), Proteus (n ϭ 3), Providencia (n ϭ 6), Serratia (n ϭ

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confidence: 90%

Detecting 16S rRNA Methyltransferases in Enterobacteriaceae by Use of Arbekacin

et al. 2016

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“…While studies conducted in the city of Delhi, India, reported other variants of bla NDM among E. coli isolates, i.e., bla NDM-4, bla , bla NDM-6 , bla NDM-7 and bla NDM-8 , 5,15 our study demonstrated only NDM-1 variety, which is in accordance with a study from northeast India. 16 The prevalence of NDM-1 in the present study was found to be 1.7% among the E. coli isolates from patients with CAI, majority of the strains (four out of five) being isolated from urine while there was no evidence of NDM-1 production among K. pneumoniae isolates.…”

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confidence: 92%

Carbapenemase and NDM-1 Production by Escherichia coli and Klebsiella pneumoniae from Patients belonging to a Rural Community in North India Hospitalized with CommunityAcquired Infections

Chattopadhya¹

2018

JCD

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Carbapenem-resistant Enterobacteriaceae, especially New Delhi metallo-β-lactamase type-1-producing strains, exhibit multidrug resistance, thus posing a serious public health threat for treatment of infections caused by Gram-negative bacteria. However, most of the studies on the problem have been confined to hospitalized patients from urban population. The present study was carried out to detect carbapenemase production among Escherichia coli and Klebsiella pneumoniae Isolated from rural population hospitalized with community acquired infections. A total of 296 non-repetitive isolates of E. coli and K. pneumoniae were subjected to Modified Hodge test for carbapenemase detection, Metallo-β-lactamase detection by MIC test strip MBL and molecular detection of bla NDM gene by Polymerase Chain Reaction (PCR). Twenty three (7.8%) of the 296 isolates were detected as carbapenemase producers, of which five (21.7%) were found to harbor bla NDM genes by PCR. Gene sequencing of all the five isolates revealed bla NDM-1 genes. The present study showed the prevalence of carbapenemase-producing E. coli and K. pneumoniae in the rural community of North India and spread of NDM-1.

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“…This is also the first ST448 E. coli strain harboring an NDM enzyme. Interestingly, bla NDM-5 was harbored by IncFII-type plasmids in isolates from India and the United Kingdom also bearing bla TEM-1 and rmtB genes, suggesting that bla NDM-5 genes might share a genetic platform (25,26).…”

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Molecular Characterization of bla _NDM-5 Carried on an IncFII Plasmid in an Escherichia coli Isolate from a Nontraveler Patient in Spain

Pitart

Solé

Roca

et al. 2015

Antimicrob Agents Chemother

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A carbapenem-resistant Escherichia coli isolate (sequence type 448 [ST448]) was recovered from a urine culture of a female patient with no recent record of traveling. PCR screening identified the presence of bla NDM-5 , bla TEM-1 , bla OXA-1 , bla CMY-42 , and rmtB. bla NDM-5 was carried in a conjugative IncFII-type plasmid (90 kb) together with bla TEM-1 and rmtB. The genetic environment of bla NDM-5 showed a structure similar to those of pMC-NDM and pGUE-NDM, identified in Poland and France in E. coli of African and Indian origin, respectively. C arbapenemase-producing Enterobacteriaceae (CPE) constitute a public health problem regarding both hospital-and community-acquired infections (1). Despite increasing reports of CPE in Europe, predominantly in southern European countries, the prevalence of CPE in Spain still remains relatively low although it is steadily increasing, with only a few outbreaks or sporadic isolates harboring VIM, KPC, OXA-48, or NDM-1 being reported (2). Since the identification of NDM-1 in a Swedish traveler returning from India (3), NDM enzymes have received special attention due to their rapid global spread and frequent association with additional resistance genes (4). There are currently 12 NDM variants (http://www.lahey.org), differing by one or two amino acid substitutions, that may display slightly different hydrolytic capabilities (4).The aim of this study was to characterize an NDM-5-producing Escherichia coli recovered in Spain from a nontraveler patient.A 78-year-old Spanish Caucasian female with a history of acute pyelonephritis treated with ceftriaxone (1 g/24 h) was positive for a carbapenem-resistant E. coli strain (HC105) in urine samples 15 days after the end of treatment. The patient was asymptomatic at this stage. The susceptibility testing using Etest strips (AB-bioMérieux, Solna, Sweden) and interpreted according to the EUCAST guidelines (version 4.0, 2014; http://www.eucast.org) indicated that HC105 was resistant to all of the antibiotics tested except tigecycline, fosfomycin, and colistin (MICs of 0.38 g/ml, 0.5 g/ml, and 0.125 g/ml, respectively) and had ertapenem, imipenem, and meropenem MICs of Ͼ32 g/ml (Table 1). The patient was successfully treated with fosfomycin (2 g/8 h), and no additional CPE were recovered. The screening of HC105 for carbapenemase/metallo-␤-lactamase (MBL) production using either the modified Hodge test or imipenem-EDTA Etest strips yielded positive results, suggesting carriage of an MBL. The PCR and sequence analysis for carbapenemase, extended-spectrum ␤-lactamase (ESBL), and plasmid-mediated AmpC cephalosporinaseencoding genes (5, 6) identified the presence of bla NDM-5 , bla TEM-1 , bla OXA-1 , and bla . The screening for 16S rRNA methylase genes (7) also identified the rmtB gene, conferring highlevel resistance to all aminoglycosides, in agreement with the susceptibility profile (Table 1). The multilocus sequence typing (http: //mlst.ucc.ie/mlst/dbs/Ecoli) and PCR-based phylogroup analysis (8) assigned E. coli HC105 to sequence type 4...

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Prevalence and molecular characterisation of New Delhi metallo-β-lactamases NDM-1, NDM-5, NDM-6 and NDM-7 in multidrug-resistant Enterobacteriaceae from India

Cited by 140 publications

References 26 publications

Detecting 16S rRNA Methyltransferases in Enterobacteriaceae by Use of Arbekacin

Detecting 16S rRNA Methyltransferases in Enterobacteriaceae by Use of Arbekacin

Carbapenemase and NDM-1 Production by Escherichia coli and Klebsiella pneumoniae from Patients belonging to a Rural Community in North India Hospitalized with CommunityAcquired Infections

Molecular Characterization of bla _NDM-5 Carried on an IncFII Plasmid in an Escherichia coli Isolate from a Nontraveler Patient in Spain

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Prevalence and molecular characterisation of New Delhi metallo-β-lactamases NDM-1, NDM-5, NDM-6 and NDM-7 in multidrug-resistant Enterobacteriaceae from India

Cited by 140 publications

References 26 publications

Detecting 16S rRNA Methyltransferases in Enterobacteriaceae by Use of Arbekacin

Detecting 16S rRNA Methyltransferases in Enterobacteriaceae by Use of Arbekacin

Carbapenemase and NDM-1 Production by Escherichia coli and Klebsiella pneumoniae from Patients belonging to a Rural Community in North India Hospitalized with CommunityAcquired Infections

Molecular Characterization of bla NDM-5 Carried on an IncFII Plasmid in an Escherichia coli Isolate from a Nontraveler Patient in Spain

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Molecular Characterization of bla _NDM-5 Carried on an IncFII Plasmid in an Escherichia coli Isolate from a Nontraveler Patient in Spain