scholarly journals Rising Threat of OXA-48 and other Carbapenemase Encoding Genes among Carbapenem Resistant Enterobacteriaceae in India

2020 ◽  
Vol 14 (3) ◽  
pp. 1917-1925
Author(s):  
Satyajeet K. Pawar ◽  
Shivaji T. Mohite ◽  
Kailash D. Datkhile ◽  
Madhavi N. Patil ◽  
Satish V. Kakade
Keyword(s):  
Diagnostic Methods ◽  
Contact Precautions ◽  
Carbapenem Resistant ◽  
Class D ◽  
Class B ◽  
Horizontal Spread ◽  
Phenotypic Methods ◽  
Hospital Acquired ◽  
Encoding Genes ◽  
Carbapenem Resistant Enterobacteriaceae

Members of Enterobacteriaceae family are responsible for both community and hospital acquired infections. Because of development of antimicrobial resistance carbapenem has remained as last resort of drug for treatment of infections caused by these bacteria.Mechanism for development of this resistance in carbapenem resistant Enterobacteriaceae (CRE) may due to production of carbapenemases, efflux mechanism or loss of outer membrane porins.The most common carbapenemase enzymes are Class A – KPC, Class B – NDM, VIM and IMP and Class D oxacillinase(OXA-48 like enzymes).In India, most prevalent carbapenemase encoding gene is NDM-1but there is rising threat of OXA-48 prevalence. Unlike the phenotypic methods, the genotypic methods are useful to discriminate the type of carbapenemase enzyme, specifically for OXA-48 like enzymes. Total 170 CRE isolates were subjected for multiplex PCR study for their molecular characterization. Of the 170 CRE isolates,68.2 % (n=116) were positive for NDM-1 gene while 44.1 % (n= 75) of the isolates showed presence of OXA-48 gene. VIM (2.3%), KPC (1.7 %) were responsible for carbapenemase production while none of the isolates showed presence of IMP gene. NDM-1 and OXA-48 coexisted in 21.2 % (n=36) of the total isolates. OXA-48 causes weak hydrolysis of carbapenem because of which it is under reported with routine diagnostic methods. Early detection of OXA-48 and other carbapenemase encoding genes, helps for contact precautions and effective therapy which prevents further escalation and horizontal spread of CRE.

scholarly journals Present and Future of Carbapenem-resistant Enterobacteriaceae (CRE) Infections

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 122 ◽  
Author(s):  
Suay-García ◽  
Pérez-Gracia
Keyword(s):  
Enzyme Production ◽  
Resistance Mechanism ◽  
Carbapenem Resistance ◽  
The United States ◽  
Klebsiella Pneumoniae Carbapenemase ◽  
Carbapenem Resistant ◽  
Class D ◽  
Therapeutic Guidelines ◽  
Class B ◽  
Carbapenem Resistant Enterobacteriaceae

Carbapenem-resistant Enterobacteriaceae (CRE) have become a public health threat worldwide. There are three major mechanisms by which Enterobacteriaceae become resistant to carbapenems: enzyme production, efflux pumps and porin mutations. Of these, enzyme production is the main resistance mechanism. There are three main groups of enzymes responsible for most of the carbapenem resistance: KPC (Klebsiella pneumoniae carbapenemase) (Ambler class A), MBLs (Metallo-ß-Lactamases) (Ambler class B) and OXA-48-like (Ambler class D). KPC-producing Enterobacteriaceae are endemic in the United States, Colombia, Argentina, Greece and Italy. On the other hand, the MBL NDM-1 is the main carbapenemase-producing resistance in India, Pakistan and Sri Lanka, while OXA-48-like enzyme-producers are endemic in Turkey, Malta, the Middle-East and North Africa. All three groups of enzymes are plasmid-mediated, which implies an easier horizontal transfer and, thus, faster spread of carbapenem resistance worldwide. As a result, there is an urgent need to develop new therapeutic guidelines to treat CRE infections. Bearing in mind the different mechanisms by which Enterobacteriaceae can become resistant to carbapenems, there are different approaches to treat infections caused by these bacteria, which include the repurposing of already existing antibiotics, dual therapies with these antibiotics, and the development of new ß-lactamase inhibitors and antibiotics.

scholarly journals Neonates with Maternal Colonization of Carbapenemase-Producing, Carbapenem-Resistant Enterobacteriaceae: A Mini-Review and a Suggested Guide for Preventing Neonatal Infection

Children ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 399
Author(s):  
Judy Seesahai ◽  
Paige Terrien Church ◽  
Elizabeth Asztalos ◽  
Melanee Eng-Chong ◽  
Jo Arbus ◽  
...  
Keyword(s):  
Neonatal Intensive Care ◽  
Neonatal Infection ◽  
Control Measures ◽  
Resistant Bacteria ◽  
Negative Consequences ◽  
Duration Of Treatment ◽  
Contact Precautions ◽  
Carbapenem Resistant ◽  
Carbapenem Resistant Enterobacteriaceae

Carbapenemase-producing, carbapenem-resistant Enterobacteriaceae (CP-CRE) are highly drug-resistant Gram-negative bacteria. They include New Delhi metallo-ß-lactamase (NDM)-producing carbapenemase (50.4% of all species in Ontario). Antibiotic challenges for resistant bacteria in neonates pose challenges of unknown dosing and side effects. We report two antenatally diagnosed CP-CRE colonization scenarios with the NDM 1 gene. The case involves extreme preterm twins who had worsening respiratory distress at birth requiring ventilator support, with the first twin also having cardiovascular instability. They were screened for CP-CRE, and a polymyxin antibiotic commenced. In the delivery room, neonatal intensive care unit (NICU) and the follow-up clinic, in collaboration with the interdisciplinary group, contact precautions and isolation procedures were instituted. None of the infants exhibited infection with CP-CRE. Consolidating knowledge with regard to CP-CRE and modifying human behavior associated with its spread can mitigate potential negative consequences. This relates to now and later, when travel and prolific human to human contact resumes, from endemic countries, after the current COVID-19 pandemic. Standardized efforts to curb the acquisition of this infection would be judicious given the challenges of treatment and continued emerging antibiotic resistance. Simple infection control measures involving contact precautions, staff education and parental cohorting can be useful and cost-effective in preventing transmission. Attention to NICU specific measures, including screening of at-risk mothers (invitro fertilization conception) and their probands, careful handling of breastmilk, judicious antibiotic choice and duration of treatment, is warranted. What does this study add? CP-CRE is a nosocomial infection with increasing incidence globally, and a serious threat to public health, making it likely that these cases will present with greater frequency to the NICU team. Only a few similar cases have been reported in the neonatal literature. Current published guidelines provide a framework for general hospital management. Still, they are not specific to the NICU experience and the need to manage the parents’ exposure and the infants. This article provides a holistic framework for managing confirmed or suspected cases of CP-CRE from the antenatal care through the NICU and into the follow-up clinic targeted at preventing or containing the spread of CP-CRE.

Study on Phenotypic Detection of Carbapenemase Producing Enterobacteriaceae in MBS Hospital, Kota

2021 ◽  
Vol 10 (29) ◽  
pp. 2181-2185
Author(s):  
Pooja Jain ◽  
Naveen Saxena
Keyword(s):  
Critically Ill ◽  
Multi Drug Resistance ◽  
Environmental Cleaning ◽  
Beta Lactamases ◽  
Contact Precautions ◽  
Carbapenem Resistant ◽  
Surgical Ward ◽  
Study Results ◽  
Class B

BACKGROUND The Carbapenemase Resistant Enterobacteriaceae (CRE) are associated with high rates of morbidity and mortality particularly amongst critically ill patients. Hence rapid laboratory detection of CRE hospitalized patients is highly desirable. The vast majority of carbapenemases belong to three of the four known classes of beta lactamases namely Ambler class A, Ambler class B metallobetalactamases (MBL) and Ambler class Doxacillinases (OXAs). The purpose of this study was to determine the prevalence of carbapenemases producing Enterobacteriaceae in clinical isolates in MBS hospital, Kota. METHODS This study was conducted in the Department of Microbiology at MBS Hospital, Kota from June 2020 to December 2020. 68 non repeat isolates (MDR) that were resistant to imipenem (10 mg) according to CLSI breakpoint were included in the present study. RESULTS Out of 68 imipenem resistant Enterobacteriaceae, 52 were carbapenemase producing as detected by Modified Hodge Test. As per our study, the prevalence of carbapenemase producing Enterobacteriaceae was 20.8%. Most commonly seen in K. pneumoniae isolated from urine and swab of critically ill and debilitated patients of surgical ward. CONCLUSIONS Curbing irrational usage of antimicrobials in India is urgently required. Thus, aggressive infection control efforts have been effective at decreasing rates of infections with KPC-producing bacteria in intensive care units and long-term acute care hospitals. Bundled interventions including enhanced environmental cleaning, active surveillance culturing and contact precautions, as well as antimicrobial stewardship are important in controlling KPC-producing bacteria. KEY WORDS Multi Drug Resistance Enterobacteriaceae (MDRE), Klebsiella Producing Carbapenemase (KPC), Carbapenem Resistant Enterobacteriaceae (CRE), Metallo Beta Lactamase (MBL), Modified Hodge Test (MHT)

scholarly journals Genetic Diversity, Biochemical Properties, and Detection Methods of Minor Carbapenemases in Enterobacterales

2021 ◽  
Vol 7 ◽  
Author(s):  
Rémy A. Bonnin ◽  
Agnès B. Jousset ◽  
Cécile Emeraud ◽  
Saoussen Oueslati ◽  
Laurent Dortet ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Multidrug Resistant ◽  
Biochemical Properties ◽  
Amino Acid Sequences ◽  
Detection Methods ◽  
Gram Negative ◽  
Class A ◽  
Class D ◽  
Class B ◽  
Encoding Genes

Gram-negative bacteria, especially Enterobacterales, have emerged as major players in antimicrobial resistance worldwide. Resistance may affect all major classes of anti-gram-negative agents, becoming multidrug resistant or even pan-drug resistant. Currently, β-lactamase-mediated resistance does not spare even the most powerful β-lactams (carbapenems), whose activity is challenged by carbapenemases. The dissemination of carbapenemases-encoding genes among Enterobacterales is a matter of concern, given the importance of carbapenems to treat nosocomial infections. Based on their amino acid sequences, carbapenemases are grouped into three major classes. Classes A and D use an active-site serine to catalyze hydrolysis, while class B (MBLs) require one or two zinc ions for their activity. The most important and clinically relevant carbapenemases are KPC, IMP/VIM/NDM, and OXA-48. However, several carbapenemases belonging to the different classes are less frequently detected. They correspond to class A (SME-, Nmc-A/IMI-, SFC-, GES-, BIC-like…), to class B (GIM, TMB, LMB…), class C (CMY-10 and ACT-28), and to class D (OXA-372). This review will address the genetic diversity, biochemical properties, and detection methods of minor acquired carbapenemases in Enterobacterales.

scholarly journals 1826. Impact of Rapid Diagnostics and Ceftazidime–Avibactam on Mortality after Bacteremia Caused by Carbapenem-Resistant Enterobacteriaceae

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S41-S41
Author(s):  
Michael J Satlin ◽  
Liang Chen ◽  
Gregory Weston ◽  
Angela Gomez-Simmonds ◽  
Tanaya Bhowmick ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Blood Culture ◽  
Antimicrobial Therapy ◽  
Statistical Significance ◽  
Diagnostic Methods ◽  
Source Control ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene ◽  
Definitive Therapy ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Background Patients with bloodstream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) have long delays until receipt of appropriate antimicrobial therapy and high mortality rates. Rapid molecular diagnostics and novel therapies, such as ceftazidime–avibactam (CAZ-AVI), offer promise to improve outcomes, but their clinical impact is unclear. Methods We conducted an observational study of patients with CRE BSI from January 2016 to June 2018 at 8 New York and New Jersey medical centers. Patient demographics, comorbidities, clinical presentations, diagnostic methods, and treatments were compared between patients who died within 30 days of BSI onset and survivors. Independent risk factors for mortality were identified using logistic regression. We then compared time to receipt of active antimicrobial therapy between patients whose positive blood culture bottles underwent testing for the Klebsiella pneumoniae carbapenemase gene (blaKPC PCR) and patients where this test was not used. Results We identified 178 patients with CRE BSI (K. pneumoniae: n = 104, 58%; Enterobacter cloacae: n = 26, 15%; Escherichia coli: n = 26, 15%). The 30-day mortality rate was 38%. An increasing Acute Physiology and Chronic Health Evaluation II score (adjusted odds ratio [aOR] 1.06, P = 0.005) was independently associated with increased 30-day mortality; whereas, use of blaKPC PCR (aOR 0.31, P = 0.005), urinary tract source (aOR 0.12, P = 0.001), and source control (aOR 0.25, P = 0.001) were independently associated with survival. Initial targeted therapy with CAZ-AVI was associated with a 28% 30-day mortality rate, compared with a 49% 30-day mortality rate among patients who received a polymyxin or aminoglycoside (P = 0.036). Patients whose blood culture underwent blaKPC PCR were more likely to receive active antimicrobial therapy within 24 hours of BSI onset (42% vs. 28%; P = 0.07) and had a decreased median time until receipt of active therapy (25 hours vs. 46 hours; P = 0.07), although these differences did not achieve statistical significance. Conclusion The use of PCR to rapidly identify blood cultures with blaKPC and definitive therapy with CAZ-AVI instead of polymyxins or aminoglycosides were associated with decreased mortality after CRE bacteremia. Disclosures All Authors: No reported Disclosures.

scholarly journals Comparative Evaluation of Four Phenotypic Methods for Detection of Class A and B Carbapenemase-Producing Enterobacteriaceae in China

2018 ◽  
Vol 56 (8) ◽  
Author(s):  
Menglan Zhou ◽  
Danchen Wang ◽  
Timothy Kudinha ◽  
Qiwen Yang ◽  
Shuying Yu ◽  
...  
Keyword(s):  
Predictive Value ◽  
Comparative Evaluation ◽  
Detection Sensitivity ◽  
Detection Methods ◽  
Content Type ◽  
Class A ◽  
Carbapenem Resistant ◽  
Class B ◽  
Phenotypic Methods ◽  
Sensitivity Specificity

ABSTRACT The objective of this study was to evaluate the performance of four phenotypic methods in the detection of carbapenemase-producing Enterobacteriaceae (CPE) in China. We evaluated the performance of four carbapenemase detection methods, the modified Hodge test (MHT), the Carba NP test, the meropenem hydrolysis assay (MHA) with 1- and 2-h incubation, and the modified carbapenem inactivation method (mCIM) with meropenem, imipenem, and ertapenem, on 342 carbapenem-resistant Enterobacteriaceae isolates (CRE) in China. PCR was used as the gold standard. The 2-h-incubation MHA performed the best in carbapenemase detection (overall sensitivity, specificity, positive predictive value, and negative predictive value all 100%). Second was the Carba NP test, with a sensitivity of 99.6%. The 1-h-incubation MHA performed poorly in Klebsiella pneumoniae carbapenemase (KPC) detection (sensitivity, 71.3%). For mCIM, the best performance was observed with the meropenem disk. The MHT exhibited the worst performance, with a specificity of 88.8%. All assays except 1-h-incubation MHA, which failed to identify 68 KPC-2s, had a sensitivity of >98% in the detection of 172 KPCs. Likewise, all assays had a sensitivity of >95% in the detection of 70 class B carbapenemases, except for MHT (82.9%). The 2-h-incubation MHA significantly improved the accuracy in CPE detection compared with that for 1-h incubation and performed the best in the detection of class A and B carbapenemases. Our findings suggest that the MHA is the most practical assay for carbapenemase detection. For those who cannot afford the associated equipment, both the Carba NP test and mCIM are good alternatives with regard to the practical requirements of time and cost.

Detailed characterization of an IncFII plasmid carrying blaOXA-48 from Lebanon

2020 ◽  
Vol 75 (9) ◽  
pp. 2462-2465 ◽  
Author(s):  
Jennifer Moussa ◽  
Balig Panossian ◽  
Elie Nassour ◽  
Tamara Salloum ◽  
Edmond Abboud ◽  
...  
Keyword(s):  
Rapid Identification ◽  
Complete Sequence ◽  
Conjugative Plasmid ◽  
Incompatibility Group ◽  
Carbapenem Resistant ◽  
Class D ◽  
Long Read ◽  
Important Challenge ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Background The spread of carbapenem-resistant Enterobacteriaceae is an important challenge and an increasing healthcare problem. OXA-48 is a class D carbapenemase that is usually localized on a conjugative plasmid belonging to the IncL incompatibility group. Methods In this study, we used a combination of short- and long-read WGS approaches and molecular typing techniques to characterize the genetic environment of the smallest reported 27 029 bp IncFII plasmid carrying blaOXA-48 (pLAU-OXA48). Results The plasmid recovered from a clinical Escherichia coli isolate was positive for blaOXA-48, which was located within the Tn6237 composite transposon. Primers targeting junctions between the IncF fragment and Tn6237 for the rapid identification of pLAU-OXA48-like plasmids were designed. Conclusions To our knowledge, this is the first report showing the complete sequence of an IncFII plasmid carrying blaOXA-48 within Tn6237 using hybrid assembly of long- and short-read sequencing.

scholarly journals Carbapenemase Detection among Carbapenem-Resistant Glucose-Nonfermenting Gram-Negative Bacilli

2017 ◽  
Vol 55 (9) ◽  
pp. 2858-2864 ◽  
Author(s):  
Patricia J. Simner ◽  
Belita N. A. Opene ◽  
Krizia K. Chambers ◽  
Matthew E. Naumann ◽  
Karen C. Carroll ◽  
...  
Keyword(s):  
Method Comparison ◽  
Comparison Study ◽  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Class D ◽  
Class B ◽  
Synergy Test ◽  
Method Comparison Study ◽  
Phenotypic Tests

ABSTRACT Accurate detection of carbapenemase-producing glucose-nonfermenting Gram-negative bacilli (CPNFs), including Pseudomonas aeruginosa and Acinetobacter baumannii , is necessary to prevent their dissemination within health care settings. We performed a method comparison study of 11 phenotypic carbapenemase detection assays to evaluate their accuracy for the detection of CPNFs. A total of 96 carbapenem-resistant glucose-nonfermenting isolates were included, of which 29% produced carbapenemases. All CPNFs were molecularly characterized to identify β-lactamase genes. A total of 86% of the carbapenemase-producing P. aeruginosa isolates produced class B carbapenemases. Several assays performed with a sensitivity of >90% for the detection of carbapenemase-producing P. aeruginosa , including all rapid chromogenic assays and the modified carbapenem inactivation method. Most included assays, with the exception of the Manual Blue Carba assay, the Modified Carba NP assay, the boronic acid synergy test, and the metallo-β-lactamase Etest, had specificities of >90% for detecting carbapenemase-producing P. aeruginosa . Class D carbapenemases were the most prevalent carbapenemases among the carbapenemase-producing A. baumannii strains, with 60% of the carbapenemase-producing A. baumannii isolates producing acquired OXA-type carbapenemases. Although several assays achieved >90% specificity in identifying carbapenemase-producing A. baumannii , no assays achieved a sensitivity of greater than 90%. Our findings suggest that the available phenotypic tests generally appear to have excellent sensitivity and specificity for detecting carbapenemase-producing P. aeruginosa isolates. However, further modifications to existing assays or novel assays may be necessary to accurately detect carbapenemase-producing A. baumannii .

scholarly journals Modified CIM-Test As a Useful Tool to Detect Carbapenemase Activity Among Extensively Drug- Resistant Klebsiella Pneumoniae, Escherichia Coli and Acinetobacter Baumannii

2021 ◽  
Author(s):  
Abed Zahedi bialvaei ◽  
Alireza Dolatyar Dehkharghani ◽  
Farhad Asgari ◽  
Firouzeh Shamloo ◽  
Parisa Eslami ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Acinetobacter Baumannii ◽  
Sensitivity And Specificity ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Polymerase Chain ◽  
Phenotypic Methods ◽  
Encoding Genes ◽  
Positive Results

Abstract Background Timely detection of carbapenemases is essential for developing strategies to control the spread of infections by carbapenem-resistant isolates. The purpose of our study was to determine the epidemiology of carbapenemase genes among carbapenem resistant isolates of Acinetobacter baumannii, Klebsiella pneumoniae and Escherichia coli and to compare efficacy of modified Hodge Test (MHT), Carba NP and modified carbapenem inactivation method (mCIM) tests. Methods A total of 122 carbapenem-resistant clinical isolates including 77 K. pneumoniae, 39 A. baumannii, and six E. coli were collected from hospitalized patients. Three phenotypic methods, including MHT, Carba NP test and mCIM were used for investigation of carbapenemase production. In addition, polymerase chain reaction (PCR) was performed to detect carbapenemase encoding genes. Results The sensitivity and specificity of the MHT were 75.0% and 100% respectively. In addition, CarbaNP displayed 80.8% sensitivity and 100% specificity, whereas the sensitivity and specificity were 90.4% and 100% for the mCIM test, respectively. Among carbapenem-resistant isolates, 70, 84 and 87 isolates exhibited positive results according to MHT, CarbaNP test and mCIM, respectively. PCR indicated the presence of one or more carbapenemase genes in 119 of carbapenem-resistant isolates, with blaKPC and blaVIM being the most commonly encountered. Co-production of ‘KPC and VIM’, ‘KPC and IMP’ and ‘KPC and OXA-48’ was detected in nine, seven and three isolates, respectively. Conclusion Our results confirm that the mCIM test is a useful tool for the reliable detection of carbapenemases-activity in enterobacterial isolates, especially in clinical microbiological laboratories with limited resources.

scholarly journals Phylogenetically Diverse Escherichia Coli Strains From Chicken Co-Harbour Multiple Carbapenemase Encoding Genes (blaNDM-blaOXA-blaIMP)

2020 ◽  
Author(s):  
Erkihun Aklilu ◽  
Azian Harun ◽  
Kirnpal Kaur Banga Singh ◽  
Shamsaldeen Ibrahim ◽  
Nor Fadhilah Kamaruzzaman
Keyword(s):  
Public Health ◽  
Phylogenetic Diversity ◽  
Farm Animals ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Resistance Patterns ◽  
Phylogenetic Grouping ◽  
Encoding Genes ◽  
Potential Public Health ◽  
Carbapenem Resistant Enterobacteriaceae

Carbapenem resistant Enterobacteriaceae (CRE) has been public health risk in several countries and recent reports indicate the emergence of CRE in food animals. This study was conducted to investigate the occurrence, resistance patterns, and phylogenetic diversity of CRE E.coli from chicken. Routine bacteriology, PCR detection of E.coli species, multiplex PCR to detect carbapenemase encoding genes and phylogeny of CRE E. coli were conducted. The results show that 24.36 % (19/78) were identified as CRE based on the phenotypic identifications of which 17 were positive for the tested carabanemase genes. The majority, 57.99% (11/19) of the isolates harbored multiple carbapenemase genes. Four isolates harbored all blaNDM blaOXA, blaIMP, five and two different isolates harbored blaNDM and blaOXA, and blaOXA and blaIMP respectively. The Meropenem, Imipenem and Ertapenem MIC values for the isolates ranged from 2g/mL to ≥256g/mL. Phylogenetic grouping showed that the CRE E.coli isolates belonged to five different groups; groups A, B1, C, D and unknown. The detection of carbapenem resistant E.coli in this study shows that CRE is has become an emerging problem in farm animals, particularly, in poultry farms. This also implies the potential public health risks posed by CRE from chicken to the consumers.

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