Carbapenem Resistance among Marine Bacteria—An Emerging Threat to the Global Health Sector

The emergence of antibiotic resistance among pathogenic microorganisms is a major issue for global public health, as it results in acute or chronic infections, debilitating diseases, and mortality. Of particular concern is the rapid and common spread of carbapenem resistance in healthcare settings. Carbapenems are a class of critical antibiotics reserved for treatment against multidrug-resistant microorganisms, and resistance to this antibiotic may result in limited treatment against infections. In addition to in clinical facilities, carbapenem resistance has also been identified in aquatic niches, including marine environments. Various carbapenem-resistant genes (CRGs) have been detected in different marine settings, with the majority of the genes incorporated in mobile genetic elements, i.e., transposons or plasmids, which may contribute to efficient genetic transfer. This review highlights the potential of the marine environment as a reservoir for carbapenem resistance and provides a general overview of CRG transmission among marine microbes.

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Evaluation of Tigecycline and Minocycline Susceptibility among Clinical Isolates of Carbapenem Resistant Acinetobacter Species

Journal of Evolution of Medical and Dental Sciences ◽

10.14260/jemds/2021/297 ◽

2021 ◽

Vol 10 (19) ◽

pp. 1408-1412

Author(s):

Asna Parveen ◽

Pratibha Bhat

Keyword(s):

Carbapenem Resistance ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Clinical Samples ◽

Acinetobacter Species ◽

Healthcare Settings ◽

Carbapenem Resistant ◽

Vitek 2 ◽

Key Words Carbapenem

BACKGROUND Acinetobacter species are important infectious agents worldwide especially in healthcare settings. It has the ability to develop various resistance mechanisms to various antibiotics. We wanted to study the role of tigecycline and minocycline in the treatment of multidrug resistant Acinetobacter species. METHODS 254 non-repetitive isolates of Acinetobacter species from various clinical samples like exudates, blood, sputum, urine were retrospectively studied. Antibiotic susceptibility testing was done by Vitek 2 compact system. Susceptibility of the carbapenem resistant isolates towards tigecycline and minocycline were analysed. RESULTS 205 (80.7 %) isolates were resistant to either of the carbapenem drugs and 49 (19.3 %) were sensitive to all the 3 carbapenems, namely imipenem, meropenem and doripenem. 54.1 % isolates were sensitive to tigecycline while sensitivity towards minocycline was 40.5 %. The degree of sensitive concordance in the susceptibility to minocycline and tigecycline against Acinetobacter species was 31.1 %, which indicated fair agreement statistically. 21.1 % isolates were resistant / intermediate to minocycline but sensitive to tigecycline. Only 9.4 % isolates which were resistant to tigecycline were sensitive to minocycline. CONCLUSIONS The results of the present study have demonstrated that minocycline and tigecycline are effective against the carbapenem resistant Acinetobacter species. Tigecycline can be considered as a therapeutic agent for the treatment of multidrug resistant Acinetobacter which are otherwise difficult to inhibit using other antibiotics. KEY WORDS Carbapenem Resistance, Tigecycline, Minocycline, Antimicrobial Resistance

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Phenotypic Detection of Carbapenemase Production in Carbapenem-Resistant Enterobacteriaceae by Modified Hodge Test and Modified Strip Carba NP Test

Journal of Laboratory Physicians ◽

10.1055/s-0041-1723859 ◽

2021 ◽

Author(s):

Nisha Patidar ◽

Nitya Vyas ◽

Shanoo Sharma ◽

Babita Sharma

Keyword(s):

Carbapenem Resistance ◽

Nonparametric Test ◽

Multidrug Resistant ◽

Clinical Samples ◽

Chi Square ◽

Carbapenem Resistant ◽

The Social ◽

Significant Difference ◽

High Degree ◽

Carbapenem Resistant Enterobacteriaceae

Abstract Objective Carbapenems are last resort antibiotics for multidrug-resistant Enterobacteriaceae. However, resistance to carbapenem is increasing at an alarming rate worldwide leading to major therapeutic failures and increased mortality rate. Early and effective detection of carbapenemase producing carbapenem-resistant Enterobacteriaceae (CRE) is therefore key to control dissemination of carbapenem resistance in nosocomial as well as community-acquired infection. The aim of present study was to evaluate efficacy of Modified strip Carba NP (CNP) test against Modified Hodge test (MHT) for early detection of carbapenemase producing Enterobacteriaceae (CPE). Material and Methods Enterobacteriaceae isolated from various clinical samples were screened for carbapenem resistance. A total of 107 CRE were subjected to MHT and Modified strip CNP test for the detection of CPE. Statistical Analysis It was done on Statistical Package for the Social Sciences (SPSS) software, IBM India; version V26. Nonparametric test chi-square and Z-test were used to analyze the results within a 95% level of confidence. Results Out of 107 CRE, 94 (88%) were phenotypically confirmed as carbapenemase producer by Modified strip CNP test and 46 (43%) were confirmed by Modified Hodge Test (MHT). Thirty-eight (36%) isolates showed carbapenemase production by both MHT and CNP test, 56 isolates (52%) were CNP test positive but MHT negative, eight (7%) isolates were MHT positive but CNP test negative and five (5%) isolates were both MHT and CNP test negative. There is statistically significant difference in efficiency of Modified CNP test and MHT (p < 0.05). Conclusion Modified strip CNP test is simple and inexpensive test which is easy to perform and interpret and gives rapid results in less than 5 minutes. It has high degree of sensitivity and specificity. Modified strip CNP test shows significantly higher detection capacity for carbapenemase producers as compared with MHT.

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Pseudomonas aeruginosa PAO 1 In Vitro Time–Kill Kinetics Using Single Phages and Phage Formulations—Modulating Death, Adaptation, and Resistance

Antibiotics ◽

10.3390/antibiotics10070877 ◽

2021 ◽

Vol 10 (7) ◽

pp. 877

Author(s):

Ana Mafalda Pinto ◽

Alberta Faustino ◽

Lorenzo M. Pastrana ◽

Manuel Bañobre-López ◽

Sanna Sillankorva

Keyword(s):

Pseudomonas Aeruginosa ◽

Phage Therapy ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Chronic Infections ◽

Swarming Motility ◽

Resistance Development ◽

Healthcare Settings ◽

Time Kill

Pseudomonas aeruginosa is responsible for nosocomial and chronic infections in healthcare settings. The major challenge in treating P. aeruginosa-related diseases is its remarkable capacity for antibiotic resistance development. Bacteriophage (phage) therapy is regarded as a possible alternative that has, for years, attracted attention for fighting multidrug-resistant infections. In this work, we characterized five phages showing different lytic spectrums towards clinical isolates. Two of these phages were isolated from the Russian Microgen Sextaphage formulation and belong to the Phikmvviruses, while three Pbunaviruses were isolated from sewage. Different phage formulations for the treatment of P. aeruginosa PAO1 resulted in diversified time–kill outcomes. The best result was obtained with a formulation with all phages, prompting a lower frequency of resistant variants and considerable alterations in cell motility, resulting in a loss of 73.7% in swimming motility and a 79% change in swarming motility. These alterations diminished the virulence of the phage-resisting phenotypes but promoted their growth since most became insensitive to a single or even all phages. However, not all combinations drove to enhanced cell killings due to the competition and loss of receptors. This study highlights that more caution is needed when developing cocktail formulations to maximize phage therapy efficacy. Selecting phages for formulations should consider the emergence of phage-resistant bacteria and whether the formulations are intended for short-term or extended antibacterial application.

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Using Molecular Diagnostics to Develop Therapeutic Strategies for Carbapenem-Resistant Gram-Negative Infections

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.715821 ◽

2021 ◽

Vol 11 ◽

Author(s):

Fred C. Tenover

Keyword(s):

Carbapenem Resistance ◽

Multidrug Resistant ◽

Therapeutic Strategies ◽

Beta Lactam ◽

Gram Negative ◽

Molecular Tests ◽

Negative Results ◽

Carbapenem Resistant ◽

Class B ◽

Global Threat

Infections caused by multidrug-resistant Gram-negative organisms have become a global threat. Such infections can be very difficult to treat, especially when they are caused by carbapenemase-producing organisms (CPO). Since infections caused by CPO tend to have worse outcomes than non-CPO infections, it is important to identify the type of carbapenemase present in the isolate or at least the Ambler Class (i.e., A, B, or D), to optimize therapy. Many of the newer beta-lactam/beta-lactamase inhibitor combinations are not active against organisms carrying Class B metallo-enzymes, so differentiating organisms with Class A or D carbapenemases from those with Class B enzymes rapidly is critical. Using molecular tests to detect and differentiate carbapenem-resistance genes (CRG) in bacterial isolates provides fast and actionable results, but utilization of these tests globally appears to be low. Detecting CRG directly in positive blood culture bottles or in syndromic panels coupled with bacterial identification are helpful when results are positive, however, even negative results can provide guidance for anti-infective therapy for key organism-drug combinations when linked to local epidemiology. This perspective will focus on the reluctance of laboratories to use molecular tests as aids to developing therapeutic strategies for infections caused by carbapenem-resistant organisms and how to overcome that reluctance.

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Dynamics of blaKPC-2 Dissemination from Non-CG258 Klebsiella pneumoniae to Other Enterobacterales via IncN Plasmids in an Area of High Endemicity

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01743-20 ◽

2020 ◽

Vol 64 (12) ◽

Cited By ~ 1

Author(s):

Ana M. Rada ◽

Elsa De La Cadena ◽

Carlos Agudelo ◽

Cesar Capataz ◽

Nataly Orozco ◽

...

Keyword(s):

Public Health ◽

Klebsiella Pneumoniae ◽

Neonatal Intensive Care ◽

Carbapenem Resistance ◽

Health Interventions ◽

Global Public Health ◽

Public Health Interventions ◽

Content Type ◽

Carbapenem Resistant ◽

Long Read

ABSTRACT Carbapenem-resistant Enterobacterales (CRE) pose a significant threat to global public health. The most important mechanism for carbapenem resistance is the production of carbapenemases. Klebsiella pneumoniae carbapenemase (KPC) represents one of the main carbapenemases worldwide. Complex mechanisms of blaKPC dissemination have been reported in Colombia, a country with a high endemicity of carbapenem resistance. Here, we characterized the dynamics of dissemination of blaKPC gene among CRE infecting and colonizing patients in three hospitals localized in a highly endemic area of Colombia (2013 and 2015). We identified the genomic characteristics of KPC-producing Enterobacterales recovered from patients infected/colonized and reconstructed the dynamics of dissemination of blaKPC-2 using both short and long read sequencing. We found that spread of blaKPC-2 among Enterobacterales in the participating hospitals was due to intra- and interspecies horizontal gene transfer (HGT) mediated by promiscuous plasmids associated with transposable elements that was originated from a multispecies outbreak of KPC-producing Enterobacterales in a neonatal intensive care unit. The plasmids were detected in isolates recovered in other units within the same hospital and nearby hospitals. The gene “epidemic” was driven by IncN-pST15-type plasmids carrying a novel Tn4401b structure and non-Tn4401 elements (NTEKPC) in Klebsiella spp., Escherichia coli, Enterobacter spp., and Citrobacter spp. Of note, mcr-9 was found to coexist with blaKPC-2 in species of the Enterobacter cloacae complex. Our findings suggest that the main mechanism for dissemination of blaKPC-2 is HGT mediated by highly transferable plasmids among species of Enterobacterales in infected/colonized patients, presenting a major challenge for public health interventions in developing countries such as Colombia.

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Phenotypic and genotypic characterization of multidrug-resistant isolates from patients with catheter-associated urinary tract infection in a tertiary care hospital

Journal of Laboratory Physicians ◽

10.4103/jlp.jlp_22_19 ◽

2019 ◽

Vol 11 (03) ◽

pp. 206-211

Author(s):

Jaison Jayakaran ◽

Nirupa Soundararajan ◽

Priyadarshini Shanmugam

Keyword(s):

Urinary Tract ◽

Tertiary Care Hospital ◽

Tertiary Care ◽

Carbapenem Resistance ◽

Multidrug Resistant ◽

Diffusion Method ◽

Care Hospital ◽

Disk Diffusion Method ◽

Carbapenem Resistant ◽

Tract Infections

Abstract INTRODUCTION: Urinary tract infections (UTIs) remain as the most common infection. Catheter-associated (CA) UTI can lead to bacteremia and thereby is the leading cause of morbidity and mortality in hospitalized patients in our country. AIMS AND OBJECTIVES: This study aims to check the prevalence of CAUTI and study the phenotypic and genotypic characters of the multidrug-resistant organisms in a tertiary care hospital, with special reference to NDM-1 and OXA-23. MATERIALS AND METHODS: A total of 231 urine samples from patients with CA-UTI in different wards in a tertiary care hospital over a period of 3 months between June and August 2018 were collected and processed following the standard protocol. Antibiotic susceptibility tests were performed by disk-diffusion method. Modified Hodge test (MHT) was done to isolate carbapenem-resistant isolates, and polymerase chain reaction was done to detect NDM-1 and OXA-23. RESULTS: Out of 231 samples, 101 samples yielded significant growth. These 38 samples were Gram-negative bacilli which were resistant to carbapenems. Out of the 38 which showed carbapenem resistance, 23 were MHT positive. Out of the 23 MHT-positive isolates, 8 (21.05%) were positive for NDM-1 gene and only 1 (2.6%) was positive for the OXA-23 gene. CONCLUSION: This study has shown that carbapenem-resistant isolates from all the CA urinary tract-infected patients were 52.77% and most of them were Klebsiella. About 21% of them harbored the NDM-1 gene whereas only 2% had the OXA-23 gene. There has been an alarming increase in the spread of carbapenem resistance.

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Characterization of Carbapenem-Resistant Enterobacteriaceae Cultured From Retail Meat Products, Patients, and Porcine Excrement in China

Frontiers in Microbiology ◽

10.3389/fmicb.2021.743468 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jie Feng ◽

Qian Xiang ◽

Jiangang Ma ◽

Pei Zhang ◽

Kun Li ◽

...

Keyword(s):

Meat Products ◽

Carbapenem Resistance ◽

Multidrug Resistant ◽

E Coli ◽

Carbapenem Resistant ◽

Retail Meat ◽

Different Origins ◽

Different Sources ◽

Carbapenem Resistant Enterobacteriaceae

The emergence and dissemination of carbapenem-resistant Enterobacteriaceae (CRE) is a growing concern to animal and public health. However, little is known about the spread of CRE in food and livestock and its potential transmission to humans. To identify CRE strains from different origins and sources, 53 isolates were cultured from 760 samples including retail meat products, patients, and porcine excrement. Antimicrobial susceptibility testing was carried out, followed by phylogenetic typing, whole-genome sequencing, broth mating assays, and plasmids analyses. Forty-three Escherichia coli, nine Klebsiella pneumoniae, and one Enterobacter cloacae isolates were identified, each exhibiting multidrug-resistant phenotypes. Genetically, the main sequence types (STs) of E. coli were ST156 (n = 7), ST354 (n = 7), and ST48 (n = 7), and the dominant ST of K. pneumoniae is ST11 (n = 5). blaNDM–5 (n = 40) of E. coli and blaKPC–2 (n = 5) were the key genes that conferred carbapenem resistance phenotypes in these CRE strains. Additionally, the mcr-1 gene was identified in 17 blaNDM-producing isolates. The blaNDM–5 gene from eight strains could be transferred to the recipients via conjugation assays. Two mcr-1 genes in the E. coli isolates could be co-transferred along with the blaNDM–5 genes. IncF and IncX3 plasmids have been found to be predominantly associated with blaNDM gene in these strains. Strains isolated in our study from different sources and regions tend to be concordant and overlap. CRE strains from retail meat products are a reservoir for transition of CRE strains between animals and humans. These data also provide evidence of the dissemination of CRE strains and carbapenem-resistant genes between animal and human sources.

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Genotypic Characterisation of Multi Drug Resistant Gram-Negative Bacteria with Special Reference to Carbapenem Resistance in a Teaching Hospital, Hyderabad, Telangana State

Journal of Evolution of Medical and Dental Sciences ◽

10.14260/jemds/2021/222 ◽

2021 ◽

Vol 10 (14) ◽

pp. 1039-1041

Author(s):

Swathi Gurajala ◽

Sandeep Kumar Tipparthi ◽

Rajkumar H.R.V.

Keyword(s):

Carbapenem Resistance ◽

Multidrug Resistant ◽

Control Measures ◽

Infection Prevention And Control ◽

Resistant Bacteria ◽

Antimicrobial Drug Resistance ◽

Carbapenem Resistant ◽

Carbapenemase Gene ◽

Prevention And Control Measures ◽

And Control

Bacteria develop antimicrobial drug resistance through several mechanisms, the common one being the production of enzymes. As the number of antibiotics discovered is in notable numbers in the past few years, it is important to preserve high-end antibiotics for the treatment of multidrug-resistant organisms (MDROs) infections, by appropriate use of antibiotics. A study was conducted to record prevalence, phenotypic and genotypic characters of MDROs in our hospital, with reference to carbapenem resistance. 200 multidrug-resistant clinical isolates were collected in 6 months. Carbapenem-resistant organisms were detected phenotypically confirmed for the production of carbapenemases by modified Hodge test (MHT) and genotypic detection was done by a multiplex polymerase chain reaction (PCR) assay for the five most predominant carbapenemases (bla NDM-1, bla OXA-48 , bla VIM, bla IMP, bla KPC). The isolates consisted of E. coli (53 %) followed by K. pneumoniae (30 %), P. aeruginosa (13 %), and acinetobacter spp (4 %). Among these, 40 (20 %) isolates were carbapenem-resistant. Of these 40, 27 (67.5 %) showed an increase in zone size by the MHT, suggestive of metallo-beta-lactamase (MBL) mediated carbapenem resistance and about 32 (80 %) isolates were found to contain at least one carbapenemase gene. bla NDM-1 accounted for 37.5 % (12 / 32) of the isolates and was the most predominant one followed by bla OXA-48 [28 % (9 / 32)]. 22 % (7 / 32) of the isolates had one or more carbapenemase genes. Identifying the mechanisms of resistance of pathogens is important to implement strict infection prevention and control measures in the hospital to prevent the transmission of the resistant pathogens. KEY WORDS Multidrug-Resistant Bacteria, Bla NDM-1 Gene, Bla OXA-48 Gene, Carbapenem Resistance, Carbapenem Resistant Organisms.

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Ceftazidime–avibactam and ceftolozane–tazobactam susceptibility of multidrug resistant Pseudomonas aeruginosa strains in Hungary

Acta Microbiologica et Immunologica Hungarica ◽

10.1556/030.2020.01152 ◽

2020 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Dustin O'Neall ◽

Emese Juhász ◽

Ákos Tóth ◽

Edit Urbán ◽

Judit Szabó ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Inhibitory Concentration ◽

Carbapenem Resistance ◽

Multidrug Resistant ◽

Test Results ◽

Diffusion Test ◽

Microdilution Method ◽

Carbapenem Resistant ◽

Gradient Diffusion ◽

Broth Microdilution Method

Abstract Our objective was to compare the activity ceftazidime-avibactam (C/A) and ceftolozane–tazobactam (C/T) against multidrug (including carbapenem) resistant Pseudomonas aeruginosa clinical isolates collected from six diagnostic centers in Hungary and to reveal the genetic background of their carbapenem resistance. Two hundred and fifty consecutive, non-duplicate, carbapenem-resistant multidrug resistant (MDR) P. aeruginosa isolates were collected in 2017. Minimal inhibitory concentration values of ceftazidime, cefepime, piperacillin/tazobactam, C/A and C/T were determined by broth microdilution method and gradient diffusion test. Carbapenem inactivation method (CIM) test was performed on all isolates. Carbapenemase-encoding blaVIM, blaIMP, blaKPC, blaOXA-48-like and blaNDM genes were identified by multiplex PCR. Of the isolates tested, 33.6& and 32.4& showed resistance to C/A and C/T, respectively. According to the CIM test results, 26& of the isolates were classified as carbapenemase producers. The susceptibility of P. aeruginosa isolates to C/A and C/T without carbapenemase production was 89& and 91&, respectively. Of the CIM-positive isolates, 80& were positive for blaVIM and 11& for blaNDM. The prevalence of Verona integron-encoded metallo-beta-lactamase (VIM)-type carbapenemase was 20.8&. NDM was present in 2.8& of the isolates. Although the rate of carbapenemase-producing P. aeruginosa strains is high, a negative CIM result indicates that either C/A or C/T could be effective even if carbapenem resistance has been observed.

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Emergence of DIM-1 and KPC-1 Genes Associated Carbapenem-Resistant Pseudomonas Aeruginosa Isolates in Three Major Hospitals in Hanoi, Vietnam (2010-2015)

10.21203/rs.3.rs-143498/v1 ◽

2021 ◽

Author(s):

Tran Hai Anh ◽

Tran Huy Hoang ◽

Vu Thi Ngoc Bich ◽

Trinh Son Tung ◽

Tran Dieu Linh ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Treatment Options ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Phylogenetic Tree Analysis ◽

Antibiotic Resistant ◽

Hospital Acquired Infection ◽

Healthcare Settings ◽

Carbapenem Resistant ◽

Hospital Acquired

Abstract Background: Multidrug-resistant bacteria including carbapenem resistant Pseudomonas aeruginosa are recognised as an important cause of hospital-acquired infections worldwide. To determine the molecular characterisation and antibiotic resistant genes associated with carbapenem-resistant P. aeruginosa. Methods: we conducted whole-genome sequencing and phylogenetic analysis of 72 carbapenem-resistant P. aeruginosa isolated from hospital-acquired infection patients from 2010 to 2015 in three major hospitals in Hanoi, Vietnam. Results: We identified three variants of IMP genes, among which IMP-15 gene was the most frequent (n= 34) in comparison to IMP-26 (n= 2) and IMP-51 (n=12). We observed two isolates with imipenem MIC >128mg/L that co-harboured IMP-15 and DIM-1 genes and seven isolates (imipenem MIC> 128mg/L) with KPC-1 gene from the same hospital. MLST data showed that sequence types (ST) of 72 isolates were classified into 18 STs and phylogenetic tree analysis divided these isolates into nine groups. Conclusion: Our results provide evidence that not only IMP-26, but other variants of IMPs like IMP-15 and IMP-51 genes and several STs (ST235, ST244, ST277, ST310, ST773 and ST3151) have been disseminated in health care settings in Vietnam. Also, we report the first finding in Vietnam that two isolates belonging to ST1240 and ST3340 harboured two important carbapenemase genes (IMP-15 and, DIM-1) and seven isolates belonging to ST3151 of P. aeruginosa carried the KPC-1 gene, which could be a potential cause of seriously restricted available treatment options in healthcare settings.

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