2411. Expanded Susceptibility and Resistance Mechanism Testing Among Carbapenem-Resistant Enterobacteriaceae in Connecticut, 2017

Background: Over the past decade, numbers of Carbapenemase Producing-Carbapenem Resistant Enterobacteriaceae (CP-CRE) has been increasing worldwide and it has been becoming a threat because of its resistance against carbapenem which is considered as the “last resort” antibiotic. Therapy options for its infection are still limited. Aminoglycoside serves as one of the most commonly used antibiotics, but the resistance against it has already been presented for a long time. Aminoglycoside Modifying Enzyme (AME) is the most important resistance mechanism against aminoglycoside. AAC(6’)-Ib enzyme is one of the most common AME produced by the gram-negative bacteria.Objectives: This study wished to identify the gene of this enzyme among CRE isolated from infected Indonesian patients in Dr. Mohammad Hoesin Hospital Palembang.Methods: Twenty-eight isolates collected from CRE-infected patients identified by Vitek 2 Compact (bioMerieux, USA) in dr. Mohammad Hoesin Hospital Palembang during September—November 2017. AAC(6’)-Ib gene was identified using PCR method, then visualize by electrophoresis. The result is then analyzed by comparing it with a susceptibility test. Results: Out of 28 samples, AAC(6’)-Ib is identified in 22 (78.57%) samples. Samples with AAC(6’)-Ib showed to be less resistant to various antibiotics, significantly to amikacin (p=0.023).Conclusion: AAC(6’)-Ib gene is found in most of samples implying its frequent occurrence in Indonesian patients.

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NDM Production as a Dominant Feature in Carbapenem-Resistant Enterobacteriaceae Isolates from a Tertiary Care Hospital

Antibiotics ◽

10.3390/antibiotics11010048 ◽

2021 ◽

Vol 11 (1) ◽

pp. 48

Author(s):

Fakhur Uddin ◽

Syed Hadi Imam ◽

Saeed Khan ◽

Taseer Ahmed Khan ◽

Zulfiqar Ahmed ◽

...

Keyword(s):

Tertiary Care Hospital ◽

Tertiary Care ◽

Resistance Mechanism ◽

Enterobacter Cloacae ◽

Care Hospital ◽

Healthcare Settings ◽

Carbapenem Resistant ◽

Potential Source ◽

Dominant Feature ◽

Carbapenem Resistant Enterobacteriaceae

The worldwide spread and increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE) is of utmost concern and a problem for public health. This resistance is mainly conferred by carbapenemase production. Such strains are a potential source of outbreaks in healthcare settings and are associated with high rates of morbidity and mortality. In this study, we aimed to determine the dominance of NDM-producing Enterobacteriaceae at a teaching hospital in Karachi. A total of 238 Enterobacteriaceae isolates were collected from patients admitted to Jinnah Postgraduate Medical Centre (Unit 4) in Karachi, Pakistan, a tertiary care hospital. Phenotypic and genotypic methods were used for detection of metallo-β-lactamase. Out of 238 isolates, 52 (21.8%) were CRE and 50 isolates were carbapenemase producers, as determined by the CARBA NP test; two isolates were found negative for carbapenemase production by CARB NP and PCR. Four carbapenemase-producing isolates phenotypically appeared negative for metallo-β-lactamase (MBL). Of the 52 CRE isolates, 46 (88.46%) were blaNDM positive. Most of the NDM producers were Klebsiella pneumoniae, followed by Enterobacter cloacae and Escherichia coli. In all the NDM-positive isolates, the blaNDM gene was found on plasmid. These isolates were found negative for the VIM and IPM MBLs. All the CRE and carbapenem-sensitive isolates were sensitive to colistin. It is concluded that the NDM is the main resistance mechanism against carbapenems and is dominant in this region.

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Comparing the Outcomes of Patients With Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Bacteremia

Clinical Infectious Diseases ◽

10.1093/cid/ciw741 ◽

2016 ◽

Vol 64 (3) ◽

pp. 257-264 ◽

Cited By ~ 135

Author(s):

Pranita D Tamma ◽

Katherine E Goodman ◽

Anthony D Harris ◽

Tsigereda Tekle ◽

Ava Roberts ◽

...

Keyword(s):

Antibiotic Treatment ◽

Resistance Mechanism ◽

Severity Of Illness ◽

Carbapenem Resistance ◽

Resistance Mechanisms ◽

P Value ◽

Carbapenem Resistant ◽

Type 3 ◽

Encoding Genes ◽

Carbapenem Resistant Enterobacteriaceae

Abstract Background Carbapenem-resistant Enterobacteriaceae (CRE) are associated with considerable mortality. As mechanisms of carbapenem resistance are heterogeneous, it is unclear if mortality differs based on resistance mechanisms. We sought to determine whether CRE resistance mechanism determination is prognostically informative. Methods We conducted an observational study comparing 14-day mortality between patients with carbapenemase-producing (CP)-CRE compared with non-CP-CRE bacteremia. Clinical data were collected on all patients. A comprehensive DNA microarray-based assay was performed on all isolates to identify β-lactamase-encoding genes. Results There were 83 unique episodes of monomicrobial CRE bacteremia during the study period: 37 (45%) CP-CRE and 46 (55%) non-CP-CRE. The majority of CP-CRE isolates were blaKPC (92%), followed by blaNDM (5%) and blaOXA-48-type (3%). CP-CRE isolates were more likely to have meropenem minimum inhibitory concentrations (MICs) ≥16 µg/mL, while non-CP-CRE isolates were more likely to have meropenem MICs ≤1 µg/mL (P value < .001). A total of 18 (22%) patients died within 14 days, including 12 (32%) in the CP-CRE group and 6 (13%) in the non-CP-CRE group. Adjusting for severity of illness on day 1 of bacteremia, underlying medical conditions, and differences in antibiotic treatment administered, the odds of dying within 14 days were more than 4 times greater for CP-CRE compared with non-CP-CRE bacteremic patients (adjusted odds ratio, 4.92; 95% confidence interval, 1.01–24.81). Conclusion Our findings suggest that CP-CRE may be more virulent than non-CP-CRE and are associated with poorer outcomes. This underscores the added importance of delineating underlying resistance mechanisms of CRE to direct antibiotic treatment decisions.

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Epidemiologic Patterns and Clinical Implications of Genotypic Resistance Mechanism for Carbapenem-Resistant Enterobacteriaceae (CRE)Surveillance Isolates from Los Angeles County

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.653 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S288-S288

Author(s):

Sandeep Bhaurla ◽

James A Mckinnell ◽

Patricia Marquez ◽

Marcelo Moran ◽

Audrey Manalo ◽

...

Keyword(s):

Los Angeles ◽

Los Angeles County ◽

Resistance Mechanism ◽

Clinical Implications ◽

Genotypic Resistance ◽

Carbapenem Resistant ◽

Carbapenem Resistant Enterobacteriaceae

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

Antibiotics ◽

10.3390/antibiotics8030122 ◽

2019 ◽

Vol 8 (3) ◽

pp. 122 ◽

Cited By ~ 17

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.

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518. Comparing the Mortality of Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Bacteremia

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.587 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S249-S250

Author(s):

Hyeonji Seo ◽

Eunmi Yang ◽

Seongman Bae ◽

Hyemin Chung ◽

Eunbeen Cho ◽

...

Keyword(s):

Risk Factors ◽

Combination Therapy ◽

Resistance Mechanism ◽

Carbapenem Resistance ◽

Source Control ◽

Definitive Treatment ◽

Clinical Issue ◽

Carbapenem Resistant ◽

Independent Risk Factors ◽

Carbapenem Resistant Enterobacteriaceae

Abstract Background Carbapenem-resistant Enterobacteriaceae (CRE) infection is an emerging clinical issue. One of the mechanisms of carbapenem-resistance is carbapenemase production. This study aimed to identify whether clinical outcomes differ by CRE resistance mechanism and to evaluate risk factors for mortality in patients with CRE bacteremia. Methods We conducted a retrospective cohort study comparing 14-day mortality between patients with carbapenemase-producing (CP)-CRE and non-CP-CRE bacteremia during January 2011 to October 2018. Only monomicrobial Escherichia coli or Klebsiella pneumoniae bacteremia were included in the study. A modified carbapenem inactivation method was used for phenotypic detection of carbapenemase production. The presence of a variety of carbapenemase genes was evaluated by PCR with specific primers. Results Of 134 patients with monomicrobial CRE bacteremia, 48 (35.8%) were infected with CP-CRE, and 86 (64.1%) were infected with non-CP-CRE. The most common carbapenemase in CP-CRE isolates was KPC (66.7%), followed by NDM-1 (18.8%), OXA-48-like (10.4%), and VIM (4.1%). Baseline characteristics were similar between the two groups (Table 1). However, the CP-CRE group was significantly more likely to undergo removal of eradicable foci and to have meropenem MIC >8 µg/mL. A total of 33 (24.6%) patients died within 14 days, including 9 (18.8%) in the CP-CRE group and 24 (27.9%) in the non-CP-CRE group. Deceased patients were more likely to have a higher Pitt bacteremia score, nosocomial acquisition, ineradicable or not-eradicated foci, immunosuppressant use, inappropriate definitive treatment (Table 2). Combination therapy for definitive treatment was associated with decreased mortality. In a multivariate analysis including carbapenemase production, a higher Pitt bacteremia score (aOR, 5.15), ineradicable or not-eradicated foci (aOR, 4.05) and combination therapy for definitive treatment (aOR, 0.35) were independent risk factors for mortality. Conclusion Our study suggests that carbapenemase production is not a mortality risk factor in CRE bacteremia and provides additional evidence for early source control and combination therapy. Disclosures All authors: No reported disclosures.

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