Emergence and clonal expansión of Klebsiella pneumoniae ST307, simultaneously producing KPC-3 and NDM-1

Abstract MDR Klebsiella pneumoniae ST307 is a high-risk clone, whose genetic features contribute to its adaptation to hospital environments and the human host. This study describesthe emergence and clonal dissemination of K. pneumoniae ST307, recovered during November2018 to February 2019 in a hospital in Buenos Aires city, which concurrently harbored KPC-3and NDM-1. These isolates were resistant to all -lactams and to the ceftazidime/avibactamcombination. Molecular studies showed that blaKPC-3was located in Tn4401a platform, whileblaNDM-1was surrounded upstream by ISKpn14 followed by a partial sequence of ISAba125 anddownstream by bleMBL-trpF, located in a 145.5 kb conjugative plasmid belonging to the Inc A/Cgroup. The dissemination of K. pneumoniae ST307 isolates co-producing KPC-3 and NDM-1 couldlead to a worrisome scenario due to the remarkable features of this clone and its resistanceprofile.

Resumen Klebsiella pneumoniae ST307 es un clon de alto riesgo, cuyas características genéticas contribuyen a su adaptación al entorno hospitalario y al huésped humano. Este estudio describe la emergencia y diseminación clonal de aislamientos de K. pneumoniae ST307 productores de KPC-3 y NDM-1, recuperados en un hospital de Buenos Aires. Estos aislamientos fueron resistentes a todos los p-lactámicos y a la combinación ceftacidima/avibactam. Los estudios moleculares evidenciaron que el contexto genético de blaKPC-3 se correspondió con el Tn4401a, mientras que blaNDM-1 estuvo flanqueado corriente arriba por ISKpn14 y una secuencia parcial de ISAba125 y corriente abajo por bleMBL - trpF, localizado a su vez en un plásmido conjugativo de 145.5 kb perteneciente al grupo Inc A/C. La emergencia de aislamientos de K. pneumoniae ST307 coproductores de KPC-3 y NDM-1 pone de manifiesto una situación altamente preocupante debido a las características de este clon y a su perfil de multirresistencia.

DETECTION OF CARBAPENEMASE PRODUCING ENTEROBACTERALES AMONG THE CLINICAL ISOLATES OF DIARRHOEAGENIC ESCHERICHIA COLI CAUSING ACUTE GASTROENTERITIS IN CHILDREN BELOW 2 YEARS IN TERTIARY CARE HOSPITAL OF NORTH EAST INDIA.

Introduction: Enterobacterales that test resistant to at least one of the carbapenem antibiotics (ertapenem, meropenem, doripenem, or imipenem) are called Carbapenem resistant Enterobacterales (CRE) and if they produce a carbapenemase (an enzyme that can make them resistant to carbapenem antibiotics) they are called Carpenemase producing Enterobacterales (CPE). Children with CRE strains in fecal samples are considered as a high risk group by World Health Organization (WHO), which can spread CRE by intimate contact and travel. This cross-sectional study was conducted in the Departm Methods: ent of Microbiology, RIMS, Imphal, Manipur, India from Jan 2020 to Feb 2022. A total of 157 children under 2 years of age whose stool culture was positive for diarrhoeagenic Escherichia coli were included in the study. The modified carbapenem inactivation method (mCIM) has been done for detection of carbapenemase producers and the addition of EDTA in eCIM to further differentiate between serine and metallo-?-lactamase producers. Out of 157 Result and Discussion: Diarrhoegenic E.coli (DEC) ,Carbapenem resistance was seen in 9 isolates i.e 5.7 %. Out of these 9 isolates, 3 were MBL producers tested by the phenotypic test mCIM and eCIM. All the three MBL producers carried bla NDM-1 gene. mCIM/eCIM assay is designed to simultaneously detect and distinguish the different types of carbapenemases. Carbapenemase genes are often located on plasmids that can be exchanged between Enterobacteriaceae and other Gram-negative bacteria. Carbapenem-resistant K. pneumoniae are currently more frequent and more likely to cause healthcareassociated outbreaks, carbapenem-resistant E. coli pose a greater risk for spread in the community. Conclusion: Screening for carbapenemase producer using mCIM and eCIM essay is important along with infection control measure such as active surveillance through rectal screening for CRE carriage on hospital admission, contact precautions, hand hygiene, patient isolation, environmental sanitation, case notification/fiagging, antibiotic restriction.

Primeros aislados de Enterobacter cloacae complex co-productores de KPC y NDM en un hospital de segundo nivel en la Cuidad de Panamá / First isolates of Enterobacter cloacae complex co-producing KPC and NDM in a second level hospital in City of Panama

Resumen La aparición de Enterobacterales co-productores de dos o más carbapenemasas han despertado las alertas sanitarias en Latinoamérica. Las enterobacterias co-productoras de carbapenemasas KPC y NDM-1 son resistentes a casi todos los antibacterianos existentes. Panamá ha reportado la presencia de carbapenemasas KPC desde 2010 y NDM desde 2011; sin embargo, Enterobacterales con doble producción de carbapenemasas es un fenómeno reciente en nuestros hospitales. Presentamos los dos primeros aislados de Enterobacter cloacae complex co-productores de KPC y NDM, en un hospital de segundo nivel de la Ciudad de Panamá. El reforzamiento de los sistemas de vigilancia epidemiológica en los hospitales permite realizar una detección oportuna de estas nuevas combinaciones de mecanismos de resistencia; para así, implementar medidas de prevención y control de brotes.

Abstract Enterobacterales co-producing carbapenemases have awakened health alerts in Latin America. Carbapenemase-producing Enterobacterales harboring KPC and NDM-1 are resistant to almost all existing antibiotics. Panama reports KPC since 2010, and NDM since 2011, however, Enterobacterales with double carbapenemase production is new to our hospitals. We present the first two isolates of Enterobacter cloacae complex co-producing KPC and NDM, in a second level hospital in Panama City. Strengthening epidemiological surveillance systems in hospitals allows to carry out timely detection of these new combinations of resistance; to implement outbreak prevention and control measures.

NDM-beta-lactamase-1: Where do we stand?

Multidrug-resistant (MDR) Gram-negative bacilli (GNB) have been playing havoc in the field of nosocomial as well as community-acquired infections. Of particular concern are the carbapenem-resistant GNBs, belonging to Enterobacteriaceae and encoding for New Delhi metallo-beta-lactamase-1 (NDM-1) gene. These strains spread rapidly and horizontally in the population, thus exhibiting MDR traits as these can harbour several resistance encoding genes to almost all antimicrobial groups. Several predisposing factors are responsible towards its spread, viz. excessive antibiotic usage, improper aseptic conditions by healthcare workers, lack of awareness, abruptly discontinuing medication course, alternative medications and vector-borne factors contributing to the unchecked harbouring of these super bugs in India. Thus, a bugle call has already been sounded worldwide especially in India, where the country has taken serious cognizance to build up strategy via implementation of several national programs to combat antimicrobial resistance covering human, animal, agriculture and environmental aspects. As there is an exponential rise in variants of NDM-1 harbouring strains, molecular epidemiological investigations of these strains using genotyping techniques are of paramount importance for a better understanding of this rampant spread and curbing resistance thereafter. This review explores the urgent need to develop a cost-effective, rapid molecular assay, viz. the loop-mediated isothermal amplification method for field detection of MBL harbouring bacterial strains, especially NDM-1 and its variants, thus targeting specific carbapenemase genes at a grass root level even to the remote and rural regions of the country.

Detección fenotípica y genotípica de la producción de carbapenemasas tipo NDM-1 y KPC en enterobacterias aisladas en un laboratorio clínico en Maracay, Venezuela / Phenotypic and genotypic detection of the production of carbapenemases type NDM-1 and KPC in isolated Enterobacteriaceae in a clinical laboratory in Maracay, Venezuela

INTRODUCCIÓN: La producción de beta-lactamasas capaces de hidrolizar a los carbapenémicos es uno de los mecanismos de resistencia más preocupantes porque eliminan la última opción terapéutica frente a los microorganismos multi-resistentes. OBJETIVO: Determinar la producción de carbapenemasas tipo KPC y NDM-1, empleando métodos fenotípicos y genotípicos, en enterobacterias aisladas en un laboratorio clínico de la ciudad de Maracay, Venezuela. MÉTODOS: Se determinó la producción de carbapenemasas mediante métodos fenotípicos (según algoritmo de Malbrán) y genotípicos (amplificación de los genes blaNDM-1 y blaKPC por RPC) en enterobacterias aisladas en un laboratorio clínico durante el período marzo-agosto 2018. RESULTADOS: Se identificaron 605 enterobacterias de diferentes especies, siendo Escherichia coli la cepa con mayor porcentaje de aislamiento (61,3%), seguida por Klebsiella pneumoniae (14,9%). Diez y seis enterobacterias (2,64%) fueron positivas para la producción de carbapenemasas: 13 cepas de K. pneumoniae y tres del complejo Enterobacter cloacae. La RPC demostró que 14 cepas (87,5%) contienen el gen blaNDM-1 y dos (12,5%) el gen blaKPC; se observó 100% de concordancia entre la determinación fenotípica y la RPC para ambos grupos de enzimas. CONCLUSIONES: Los resultados mostraron mayor incidencia de la metalo-beta-lactamasa tipo NDM-1, reconocida como una alarma epidemiológica debido a que su rápida diseminación dificulta su control, por lo que la identificación del tipo de enzima permitiría establecer estrategias de manejo y control más certeras con la finalidad de erradicar a dichos patógenos.

BACKGROUND: The production of carbapenem-hydrolyzing beta-lactamases is one of the most concerning resistance mechanisms since it eliminates the last therapeutic option against multidrug resistant microorganisms. AIM: To determine the production of KPC and NDM-1 type carbapenemases, using phenotypic and genotypic methods, in isolated enterobacteria in a clinical laboratory in the city of Maracay, Venezuela. METHODS: The production of carbapenemases was determined by phenotypic (according to the Malbrán algorithm) and genotypic methods (amplification of the blaNDM-1 and blaKPC genes by PCR) in clinical isolates of Enterobacteriaceae during the period March-August 2018. RESULTS: 605 Enterobacteriaceae of different species were identified, being Escherichia coli the strain with the highest percentage of isolation (61.3%), followed by Klebsiella pneumoniae (14.9%). Sixteen strains (2.64%) were positive for carbapenemases production: 13 strains of K. pneumoniae and three of the Enterobacter cloacae complex. PCR showed that 14 strains (87.5%) carry the blaNDM-1 gene and two strains (12.5%) the blaKPC gene; 100% agreement was observed between phenotypic determination and PCR for both groups of enzymes. CONCLUSIONS: The results of this study showed a higher incidence of metallo-beta-lactamase type NDM-1, which rapid dissemination and consequently difficult control has been cause of epidemiological alert. The identification of the type of enzyme would allow establishing more accurate management and control strategies in order to eradicate these pathogens.

Blandm-1 Gene Carriage In The Icu Of Tertiary Care Hospital In North India

BACKGROUND:- New Delhi metallo-β-lactamase 1 (NDM-1) enzyme leads to multidrug resistance and has been detected from bacteria in many countries. The study was done To detect bacteria carrying blaNDM-1 gene from intensive care unit (ICU) patients and correlate the change with increasing duration of ICU stay. METHODS:- Blood and urine samples were collected from 140 patients thrice- 0-2 days, 3-7 days and 7 days of ICU admission. All bacterial isolates resistant to meropenem were evaluated for Metallo-β-lactamase (MBL) production. blaNDM-1 gene was detected using Real Time PCR from the MBLproducers. RESULT:- Overall, 458 samples (229 each) of blood and urine were collected and 75 gram negative bacteria were isolated. From these, 46.7% (35/75) strains were found to be carbapenem resistant and blaNDM-1 gene was detected in 17.3% (13/75). CONCLUSION:- High prevalence of bacteria carrying blaNDM-1 gene was seen in ICU patients increasing the burden on healthcare.

Emergence of bla NDM-1 associated with the aac(6')-Ib-cr, acrB, cps, and mrkD genes in a clinical isolate of multi-drug resistant Klebsiella pneumoniae from Recife-PE, Brazil

Abstract INTRODUCTION: The emergence of New Delhi metallo-β-lactamase (NDM) is concernig because it reduces the antibiotic therapy options for bacterial infections. METHODS: Resistant and virulent genes from an isolate of Klebsiella pneumoniae derived from a patient with sepsis in a hospital in Recife-PE, Brazil, were investigated using PCR and DNA sequencing. RESULTS: bla NDM-1, aac(6')-Ib-cr and acrB resistance genes, and cps and mrkD virulence genes were detected. CONCLUSIONS To our knowledge, this is the first report on bla NDM-1 in Recife-PE. This detection alerts researchers to the need to control the spread of bla NDM-1 resistance gene by this bacterium in Brazil.

Earliest identification of New Delhi metallo-ß-lactamase 1 (NDM-1) in Acinetobacter pittii in Brazil

Abstract We report the occurrence in Brazil of the bla NDM-1 gene in Acinetobacter pittii, prior to the previously described first reports regarding the species Providencia rettgeri and Enterobacter hormaechei. Clinical isolates were investigated by polymerase chain reaction followed by bidirectional sequencing, and species was confirmed by 16S rDNA sequencing and matrix-assisted laser desorption-ionization time-of-flight spectrometry. A. pittii carrying bla NDM-1 was confirmed in a patient with no national or international travel history, or transfer from another hospital. The findings warn of the possibility of silent spread of bla NDM-1 to the community.

Carbapenemases in Acinetobacter baumannii: Review of their dissemination in Latin America / Carbapenemasas en Acinetobacter baumannii: Revisión de su diseminación en América Latina

Carbapenem resistance in gram-negative bacteria by production of carbapenemases is one of the most challenging issues regarding healthcare worldwide. We review the epidemiology and prevalence of carbapenemases in carbapenem-resistant Acinetobacter baumannii isolates from Latin American countries. High resistance rates to antimicrobial agents, particularly to carbapenems, are observed in this region. OXA-23 is the most widely disseminated class D-carbapenemase; it is present in all the countries of the region and is frequently associated to endemic clones CC113/CC79, CC104/CC15, CC110/ST25 and CC109/CC1. The emergence of OXA-72 and NDM-1 represents a novel finding which is observed simultaneously and without clonal relatedness in different countries, some of which are distant from one another, whereas OXA-143 is only present in Brazil. Further collaborative intraregional studies would provide a better understanding of these issues in most of the countries and thus, policies to control the spread of these isolates could be implemented.

En bacilos gram negativos, la resistencia a carbapenemes por producción de carbapenemasas es uno de los mayores problemas en la atención de la salud a nivel mundial. Reseñamos en este artículo la epidemiologia y la prevalencia de las carbapenemasas descritas en aislamientos de Acinetobacter baumannii recuperados en América Latina. En esta región se ha observado un alto porcentaje de resistencia a los antimicrobianos, particularmente a los carbapenemes. La carbapenemasa más frecuentemente descrita es OXA-23, que ha sido recuperada en todos los países de la región y fue asociada a los clones endémicos CC113/CC79, CC104/CC15, CC110/ST25 y CC109/CC1. La emergencia de OXA-72 y NDM-1 representa un nuevo hallazgo en varios países, algunos de los cuales se encuentran muy distantes entre sí. Por el momento, OXA-143 solo se recuperó de aislamientos obtenidos en Brasil. Serían necesarios estudios colaborativos dentro de la región para lograr una mejor comprensión de la resistencia a carbapenemes en Acinetobacter baumannii, a fin de poder instaurar medidas de control que eviten una mayor diseminación de esta bacteria.

Metalobetalactamasa de tipo Nueva Delhi en Risaralda (Colombia): reporte de un caso / New Dehli metallobectalamase in Risaralda (Colombia): Case report

Se presenta un caso de un hombre con diagnóstico de osteomielitis crónica con aislamiento en cultivo de hueso de Providencia rettgeri productora de carbapenemasa de tipo Nueva Delhi. El paciente presentó control de la infección por este germen con terapia antibióticacombinada con cefepime y gentamicina. Es el primer reporte de una infección por enterobacterias con este mecanismo de resistencia en la región.

We reported a case in a man with chronic osteomyelitis of an isolate of Providencia rettgeri carrying New-Delhi metallo-beta-lactamase. The isolate was obtained from the patient's bone culture. The infection was controlled with combined antibiotic therapy (cefepime and gentamicine). This is the first report of an infection produced by Enterobacteriaceae carrier of this metallo-beta-lactamase in the region.

Advances in the study of New Delhi metallo-β-lactamase 1 / 药学学报

The New Delhi metallo-β-lactamase-1 (NDM-1) was first reported in 2010, detected in a Klebsiella pneumoniae isolate from a Swedish patient of Indian origin. It has recently attracted extensive attention for its biological activities to catalyze the hydrolysis of almost all of β-lactam antibiotics. The gene for NDM-1 can spread from one strain of bacteria to another by horizontal gene transfer. The most troubling aspect is that there are currently no clinically available inhibitors to block the metallo-β-lactamase action. Therefore, there is urgent need to develop new NDM-1 inhibitors, which can protect β-lactam antibiotics from the hydrolysis effect of NDM-1. In this review, the current research, drug-assistant mechanism and potential NDM-1 inhibitors are summarized.

Characteristics and blaNDM-1 genetic environment of plasmid from Enterobacter aerogenes / 中国感染控制杂志

Objective To study plasmid-mediated transfer,plasmid replicon typing,and genetic environment of blaNDM-1 gene in Enterobacteraerogenes(E.aerogenes).Methods E.aerogenes HN-NDM0711 was used as the subject of this research,the transferable properties of plasmid were analyzed by conjugation testing,conjugant was performed stability testing,plasmid type was determined by PCR-based replicon typing (PBRT),downstream and upstream of blaNDM-1 were sequenced using chromosome walking method,genetic context was analyzed by BLASTN and BALSTP,as well as annotated using Vector NTI 11.5.1 software,sequence pipeline graph was made,the sequence was submitted to Genbank through software Banklt.Results The conjugation testing of E.aerogenes pHN-NDM0711 was positive,after positive conjugant was conducted 4-day passage,minimal inhibitory concentrations (MICs) of imipenem and meropenem to all the cloned strains didn't change,blaNDM-1 were all positive.The replicon type was IncA/C;blaNDM-1 gene was localized between ISAba14 and IS91,at upstream of the blaNDM-1,class 1 integron and Tn3 transposon were identified,class 1 integron contained a new mosaic structure of a drug-resistant resistance gene cassette.Conclusion E.aerogenes pHN-NDM071 1,bearing blaNDM-1 gene in IncA/C plasmid,derived from gene recombination under different antimicrobial selection pressure.Antimicrobial use in clinical,industrial and agricultural area should be strictly controlled,so as to reduce the emergence of such bacteria.

Detection of a strain of Enterobacter cloacae co-carrying NDM-1 and KPC-2 genes and its drug resistance / 中华临床感染病杂志

Objective To identify the drug resistance-related genes in a clinically isolated strain of Enterobacter cloacae.Methods A strain of Enterobacter cloacae was isolated from sputum of a patient with chronic obstructive pulmonary disease from the Affiliated Hospital of Xuzhou Medical University in March 2013.Modified Hodge test and metal enzyme inhibition test were performed for drug-resistant phenotype screening.Carbapenemase genes blaMUS-1, blaVIM-1, blaVIM-2, blaIMP, blaKPC-2, blaNDM-1, blaOXA-48 and blaGESwere amplified by polymerase chain reaction (PCR), and the positive products were sequenced and analyzed.Plasmid conjugation and transformation experiments were used to confirm that the resistance gene mediated by plasmids.Agar dilution method was used for antibiotic susceptibility test.Results Both modified Hodge test and metal enzyme inhibition test were positive in this strain of Enterobacter cloacae.blaNDM-1 gene and blaKPC-2 gene were detected by PCR, and further confirmed by sequencing.blaNDM-1 gene was carried by IncX plasmid with 54×103 bp, KPC-2 gene was carried by untyping plasmid with 42×103 bp.The strain was only sensitive to tetracycline (MIC=2 μg/mL) and tigecycline (MIC=1 μg/mL).The symptoms were improved after the patient was treated by tigecycline combined with Piperacillin/Tazobactam.Conclusion blaNDM-1 and blaKPC-2 genes in Enterobacter cloacae can be mediated by plasmids, and appropriate therapy for its infection should be based on the result of antibiotic susceptibility test.

Effective antimicrobial activity of Cbf-14-2 against penicillin-resistant bacteria in vitro and in vivo / 中国药科大学学报

The antibacterial activity and mechanism of the antimicrobial peptide mutant Cbf-14-2 against NDM-1 carrying recombinant bacteria (E.coli BL21 (DE3)-NDM-1) was investigated in this study.The minimum inhibitory concentration (MIC),minimum bactericidal concentration (MBC) and killing curves (KCs) in vitro were determined by the broth microdilution method.Mice septicemia model was established by interaperitotoneal injection of E.coli BL21 (DE3)-NDM-1 to evaluate the antibacterial activity of this peptide in vivo.Results showed that Cbf-14-2 exhibited a potent antibacterial activity with MIC of 16 μg/mL and killed almost all recombinant bacteria within 120 min.Meanwhile,it significantly improved the survival rate of infected mice up to 70％ with the decreasing of bacterial load in mice lung,liver,spleen and kidney.This powerful clearance ability of Cbf-14-2 against bacteria mainly related to its enhanced membrane penetration ability through neutralizing the negative charges and disrupting the integrity of the bacterial cell membrane.Therefore,Cbf-14-2 is expected to be a potential antimicrobial agent for the treatment of infection induced by multi-drug resistant bacteria,especially for the NDM-1carrying bacteria.

Clinical characteristics and antimicrobial resistance of the bloodstream infections due to NDM-1 producing Klebsiella pneumoniae in children / 中国感染与化疗杂志

Objective To investigate the clinical characteristics and antibiotic resistance of the bloodstream infections due to NDM-1 producing Klebsiella pneumoniae in children.Methods The nonduplicate carbapenem-resistant Klebsiella pneumoniae (CRKp) strains isolated from blood samples were collected in Beijing Children's Hospital from January 2011 to August 2014.Antimicrobial susceptibility was tested with broth microdilution method.PCR amplification and DNA sequencing were conducted targeting blaNDM-1 genes.Medical records were reviewed and analyzed.Results Of the 52 CRKp strains,blaNDM-1 gene was detected in 28 strains.All NDM-l-producing strains were multidrug-resistant.All the 28 isolates were resistant to penicillin,cephalosporins,piperacillin-tazobactam,and imipenem.More than 75.0％ of these NDM-1-producing strains were resistant to aztreonam,trimethoprim-sulfamethoxazole,gentamicin,and meropenem (92.9％,26/28).NDM-1-producing isolates had higher carbapenem MICs than non-NDM-1-producing isolates.Most (82.1％,23/28) of the NDM-1-producing isolates were isolated from hematology-oncology ward.The most common underlying disease was hematologic malignancy (78.6％,22/28).Febrile neutropenia was found in 20 (71.4％) patients.No difference was found between NDM-1-producing and non-NDM-1-producing CRKp infection in terms of repeated hospitalization (P=0.202),prior antibiotic use (P=0.615),underlying diseases (P=0.856),and deep venous catheter (P=0.099).After the susceptibility results were available,37 patients received carbapenembased combination regimen.The mortality did not show difference between NDM-1 producing CRKp infections and non-NDM-1-producing CRKp infections,7.1％ (2/28) vs.12.5％ (3/24),P=0.625.Conclusions The NDM-1 carbapenemase producing Klebsiella pneumoniae is emerging in this hospital.NDM-1-producing strains are resistant to multiple antimicrobial agents,associated with higher carbapenem MIC value.However,no difference was found in the clinical features between the bloodstream infections due to NDM-1-producing strain and those due to non-NDM-1-producing strains.

Detection of integrons and ISCR1 in and genotyping of NDM-1-producing Citrobacter freundii / 中国感染与化疗杂志

Objective To investigate the distribution of integrons and ISCR1 elements in NDM-l-producing Citrobacterfreundii isolates,and analyze the genotypes of these strains to understand their homology.Methods A total of 18 strains of NDM-1-producing Citrobacterfreundii were collected from the First Affiliated Hospital of Kunming Medical University during the period from June 2012 and October 2014.The isolates were identified and subjected to antimicrobial susceptibility testing with VITEK 2 System.Class Ⅰ,Ⅱ,and 1Ⅲ integrons and ISCR1 elements were detected by PCR.Clonal relatedness was assessed by pulsed field gel electrophoresis (PFGE).Results Most (77.8％,14/18) strains were positive for class Ⅰ integron conserved region,27.8％ (5/18) isolates were positive for ISCR1 conserved region.No class Ⅱ or Ⅲ integron was detected.Most (72.2％,13/18) isolates were positive for class Ⅰ integron variable region.None of the strains harbored class Ⅱ integron or ISCR1 variable region.Integron variable regions included gene cassette encoding resistance to aminoglycosides (aadA1,aadA5,aac(6')-Ib-cr) and trimethoprim-sulfamethoxazole (dfrA,dfrA15,dfrA17).PFGE revealed 17 clusters among 18 NDM-l-producing Citrobacter freundii isolates.Conclusions The clonal dissemination of NDM-l-producing Citrobacterfreundii isolates is not significant.Class I integron is prevalent in NDM-l-producing Citrobacter freundii.The presence of ISCR1 is relatively rare.The two mobile elements are not related to the spread of NDM-1 gene in this hospital.

Perfil de resistencia a antibióticos en bacterias que presentan la enzima NDM-1 y sus mecanismos asociados: una revisión sistemática / A profile of resistance in bacteria and the mechanisms associated due to the presence of the enzyme NDM-1: a systematic review

En 2008 se reportó la enzima NDM-1 que genera resistencia a carbapenémicos. Para determinar el perfil de resistencia que presentan las bacterias frente a esta enzima se adelantó una revisión sistemática. La búsqueda de artículos se realizó en diferentes bases de datos y para su selección se consideraron criterios de inclusión y exclusión obteniendo un total de 154 artículos. Se identificaron 617 casos, presentados en trece géneros bacterianos, que codifican para los cuatro mecanismos de resistencia, principalmente a betalactámicos y aminoglucósidos. Cuando se presenta la enzima, la posibilidad que haya genes asociados para la producción de resistencias es alta, generando así que se presenten mecanismos que evitan la acción del antibiótico haciendo difícil implementar un tratamiento efectivo.

In 2008 the NDM-1 enzyme was first reported, the enzyme responsible for the resistance to carbapenems. We conducted a systematic review to determine the resistance profile due to the presence of this enzyme in bacteria. We searched academic articles in principal databases resulting in the selection of 154 articles given our inclusion and exclusion criteria. 617 cases and 13 bacterial genera were reported in our sample. We find 4 resistance mechanisms which are principally resistant to beta-lactams and aminoglycosides. Hence, we have that the presence of the NDM-1 increases the likelihood of having genes that improves the bacteria's resistance dramatically. The presence of the NDM-1 induces mechanisms which impacts the effectiveness of antibiotics and appropriate treatments are difficult to find.

Anti-bacterial Effects of Baicalin on One Escherichia coli Strain Carrying NDM-1 Gene / 现代检验医学杂志

Objective To examine the bacteriostasis of baicalin against Escherichiacoli strain carrying NDM-1 gene.Methods Minimal inhibitory concentration(MIC)and minimal bactericidal concentration(MBC)were determined by broth dilution method.Synergy function was designed withcheckerboard method.Anti-infection effect in vivo of baicalin was observed in mice with bacteremia.Results In vitro antibacterial tests showed that the MIC and MBC baicalin were 8 mg/ml.Synergistic inhibitory effect was observed between baicalin and imipenem (FIC=0.125).In vivo inhibition experiments showed that ba-icalin had decreased the mortality of 25% of Escherichiacoli Strain carrying NDM-1 gene infection in mice.Conclusion Ba-icalin has antibacterial effect on NDM-1 E.coli.

Molecular Detection Of The New Delhi Metallo-B-Lactamase-1 Gene In Enterobacteriaceae Isolates In A Tertiary Medical Centre

Background: New Delhi metallo-b-lactamase-1 (NDM-1) is a relatively recent carbapenemase enzyme that inactivates all b-lactam antibiotics with the exception of aztreonam. This study aims to ascertain the baseline prevalence and antibiotic susceptibility patterns of NDM-1-producing Enterobacteriaceae in a tertiary medical center in Malaysia. Methods: Over a period of one year, all Enterobacteriaceae isolates from all clinical specimens with reduced susceptibility to at least one carbapenem and resistance to at least one third generation cephalosporin were subjected to antibiotic susceptibility testing by disk diffusion and molecular detection of the NDM-1 gene by single-target PCR followed by gel electrophoresis. Results: A total of 13,098 Enterobacteriaceae isolates were screened and 63 (0.48%) had reduced susceptibility to at least one carbapenem. Of this 63, 18 (29%) were NDM-1-positive. Of this 18, 16 (89.0%) were Klebsiella pneumoniae, one (5.5%) was Escherichia coli and one (5.5%) was Klebsiella ornithinolytica. Reduced susceptibility to at least one aminoglycoside was seen in 17 (94%) of the NDM-1-positive isolates. All 18 (100%) had reduced susceptibility to ertapenem and were resistant to all the second and third generation cephalosporin antibiotics tested. Conclusion: The prevalence of NDM-1-producing Enterobacteriaceae among all the Enterobacteriaceae isolates in our institution is low (0.14%) and screening for the NDM-1 gene is best performed using ertapenem-impregnated disks.

Emergence of Acinetobacter pittii Harboring New Delhi Metallo-beta-Lactamase Genes in Daejeon, Korea

Carbapenemase production has been reported worldwide in gram-negative bacteria, including Acinetobacter species. We detected carbapenemase-producing Acinetobacter pittii in clinical isolates in Daejeon, Korea. Twenty-one ertapenem-resistant A. pittii isolates screened with a disk diffusion method were characterized by using the Epsilon test, four multiplex PCR assays, and a multilocus sequence typing (MLST) scheme. A total of 21 A. pittii isolates harbored the metallo-beta-lactamase (MBL) gene bla(IMP-1) or bla(NDM-1). Nineteen isolates containing bla(IMP-1) were resistant to imipenem and meropenem, but two isolates harboring bla(NDM-1) were susceptible to them. The sequence types (STs) of the two New Delhi MBL (NDM-1)-producing A. pittii isolates were ST70 and ST207, which differed from the STs (ST63, ST119, ST396, and a novel ST) of the IMP-1-producing A. pittii. This is the first report on NDM-1-producing A. pittii isolates in Korea. Our results emphasize that the study of NDM-1-producing gram-negative bacteria should involve carbapenem-susceptible as well as carbapenem-resistant isolates.