Enterobacteriaceae isolates carrying the New Delhi metallo-β-lactamase gene in Yemen

Ten carbapenem-resistant Enterobacteriaceae (eight Klebsiella pneumoniae isolates and two Enterobacter cloacae) isolates from Yemen were investigated using in vitro antimicrobial susceptibility testing, phenotypic carbapenemase detection, multilocus sequence typing (MLST) and replicon typing. Carbapenemase, extended-spectrum β-lactamase (ESBL) and plasmid-mediated quinolone resistance determinant genes were identified using PCR and sequencing. All of the 10 carbapenem-resistant Enterobacteriaceae were resistant to β-lactams, tobramycin, ciprofloxacin and cotrimoxazole. Imipenem, doripenem and meropenem MICs ranged from 2 to >32 mg l−1 and ertapenem MICs ranged from 6 to >32 mg l−1. All of the K. pneumoniae isolates showed ESBL activity in phenotypic tests. Genes encoding bla NDM were detected in all strains. All K. pneumoniae strains produced CTX-M-15 ESBL and SHV β-lactamases. TEM-1 β-lactamase was detected in seven isolates. Nine isolates were qnr positive including QnrB1, QnrA1 and QnrS1, and six isolates produced AAC-6′-Ib-cr. MLST identified five different sequence types (STs): ST1399, ST147, ST29, ST405 and ST340. Replicon typing showed the presence of IncFII1K plasmids in four transformants. To the best of our knowledge, this is the first report of NDM-1-producing Enterobacteriaceae isolates in Yemen.

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Detection of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae producing NDM-1 in Lebanon

The Journal of Infection in Developing Countries ◽

10.3855/jidc.2340 ◽

2012 ◽

Vol 6 (05) ◽

pp. 457-461 ◽

Cited By ~ 22

Author(s):

Rima I El-Herte ◽

George F Araj ◽

Ghassan M Matar ◽

Maysa Baroud ◽

Zeina A Kanafani ◽

...

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

Carbapenem Resistance ◽

New Delhi ◽

Beta Lactamase ◽

The Novel ◽

First Report ◽

Carbapenem Resistant ◽

Lactamase Gene ◽

Carbapenem Resistant Enterobacteriaceae

Carbapenem resistance has been encountered globally with poor outcome of infected patients. NDM-1 (New Delhi metallo-beta-lactamase) gene containing organisms have emerged and are now spreading in all continents. This is the first report of Iraqi patients referred to Lebanon from whom carbapenem resistant Enterobacteriaceae were recovered. The genes involved in carbapenem resistance were bla-OXA-48 and the novel NDM-1. This report highlights the alarming introduction of such resistance among Enterobacteriaecae to this country.

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Characteristics of community-onset NDM-1-producing Klebsiella pneumoniae isolates

Journal of Medical Microbiology ◽

10.1099/jmm.0.067744-0 ◽

2014 ◽

Vol 63 (1) ◽

pp. 86-89 ◽

Cited By ~ 9

Author(s):

So Yeon Kim ◽

Ji-Young Rhee ◽

Sang Yop Shin ◽

Kwan Soo Ko

Keyword(s):

Genetic Structure ◽

Antimicrobial Resistance ◽

Klebsiella Pneumoniae ◽

Susceptibility Testing ◽

Sequence Type ◽

New Delhi ◽

Insertion Sequences ◽

Clone Sequence ◽

Community Onset

Multilocus sequence typing and in vitro antimicrobial susceptibility testing were performed for three community-onset New Delhi metallo-β-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae isolates from Korea. The genetic structure surrounding the bla NDM-1 gene was determined in bla NDM-1-harbouring plasmids. Three NDM-1-producing K. pneumoniae isolates were found to belong to the same clone (sequence type 340). Each of these isolates showed the same genetic structure surrounding the bla NDM-1 gene. The genes bla NDM-1, ble MBL, trpF and dsbC were flanked by two intact insertion sequences, ISAba125 and IS26, which may promote horizontal gene transfer. The bla NDM-1-harbouring plasmids conferred antimicrobial resistance to carbapenems, cephalosporins, aminoglycosides and aztreonam in transconjugants. It can be speculated that either the entire bla NDM-1-harbouring plasmids or just the part of the plasmid containing the bla NDM-1 gene may have transferred between K. pneumoniae and Escherichia coli. Following the transfer, the isolate disseminated throughout Korea. This study suggests the need for monitoring the dissemination of NDM-1-producing isolates across countries or continents due to their potential transferability via ISAba125- and IS26-associated transposons.

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In vitro Bactericidal Activities of Combination Antibiotic Therapies Against Carbapenem-Resistant Klebsiella pneumoniae With Different Carbapenemases and Sequence Types

Frontiers in Microbiology ◽

10.3389/fmicb.2021.779988 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jocelyn Qi-Min Teo ◽

Nazira Fauzi ◽

Jayden Jun-Yuan Ho ◽

Si Hui Tan ◽

Shannon Jing-Yi Lee ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Bactericidal Activity ◽

Carbapenem Resistance ◽

Polymyxin B ◽

Apparent Difference ◽

Initial Inoculum ◽

Carbapenem Resistant ◽

Limited Effectiveness ◽

Sequence Types

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is becoming increasingly problematic due to the limited effectiveness of new antimicrobials or other factors such as treatment cost. Thus, combination therapy remains a suitable treatment option. We aimed to evaluate the in vitro bactericidal activity of various antibiotic combinations against CRKP with different carbapenemase genotypes and sequence types (STs). Thirty-seven CRKP with various STs and carbapenemases were exposed to 11 antibiotic combinations (polymyxin B or tigecycline in combination with β-lactams including aztreonam, cefepime, piperacillin/tazobactam, doripenem, meropenem, and polymyxin B with tigecycline) in static time-kill studies (TKS) using clinically achievable concentrations. Out of the 407 isolate-combination pairs, only 146 (35.8%) were bactericidal (≥3 log10CFU/mL decrease from initial inoculum). Polymyxin B in combination with doripenem, meropenem, or cefepime was the most active, each demonstrating bactericidal activity in 27, 24, and 24 out of 37 isolates, respectively. Tigecycline in combination with β-lactams was rarely bactericidal. Aside from the lower frequency of bactericidal activity in the dual-carbapenemase producers, there was no apparent difference in combination activity among the strains with other carbapenemase types. In addition, bactericidal combinations were varied even in strains with similar STs, carbapenemases, and other genomic characteristics. Our findings demonstrate that the bactericidal activity of antibiotic combinations is highly strain-specific likely owing to the complex interplay of carbapenem-resistance mechanisms, i.e., carbapenemase genotype alone cannot predict in vitro bactericidal activity. The availability of WGS information can help rationalize the activity of certain combinations. Further studies should explore the use of genomic markers with phenotypic information to predict combination activity.

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Identification of Capsular Types in Carbapenem-Resistant Klebsiella pneumoniae Strains bywzcSequencing and Implications for Capsule Depolymerase Treatment

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03560-14 ◽

2014 ◽

Vol 59 (2) ◽

pp. 1038-1047 ◽

Cited By ~ 54

Author(s):

Yi-Jiun Pan ◽

Tzu-Lung Lin ◽

Yi-Tsung Lin ◽

Po-An Su ◽

Chun-Tang Chen ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Vaccine Development ◽

Survival Rates ◽

Multidrug Resistant ◽

Enzyme Treatment ◽

Capsular Type ◽

Content Type ◽

Carbapenem Resistant ◽

Sequence Types

ABSTRACTKlebsiella pneumoniaeis an important human pathogen associated with a variety of diseases, and the prevalence of multidrug-resistantK. pneumoniae(MDRKP) is rapidly increasing. Here we determined the capsular types of 85 carbapenem-resistantK. pneumoniae(CRKP) strains bywzcsequencing and investigated the presence of carbapenemases and integrons among CRKP strains. Ten CRKP strains (12%) were positive for carbapenemase (imipenemase, 6/85 strains;K. pneumoniaecarbapenemase, 3/85 strains; Verona integron-encoded metallo-β-lactamase, 1/85 strains). Capsular type K64 accounted for 32 CRKP strains (38%), followed by K62 (13%), K24 (8%), KN2 (7%), and K28 (6%). Sequence types (STs) were determined by multilocus sequence typing (MLST), and the results indicated that ST11, which accounted for 47% of these CRKP strains (40/85 strains), was the major ST. We further isolated a K64-specific capsule depolymerase (K64dep), which could enhance serum and neutrophil killingin vitroand increase survival rates for K64K. pneumoniae-inoculated mice. The toxicity study demonstrated that mice treated with K64dep showed normal biochemical parameters and no significant histopathological changes of liver, kidney, and spleen, indicating that enzyme treatment did not cause toxicity in mice. Therefore, the findings of capsular type clustering among CRKP strains and effective treatment with capsule depolymerase for MDRKP infections are important for capsule-based vaccine development and therapy.

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Emergence and Spread of Carbapenem-Resistant and Aminoglycoside-Panresistant Enterobacter cloacae Complex Isolates Coproducing NDM-Type Metallo-β-Lactamase and 16S rRNA Methylase in Myanmar

mSphere ◽

10.1128/msphere.00054-20 ◽

2020 ◽

Vol 5 (2) ◽

Cited By ~ 1

Author(s):

Satoshi Oshiro ◽

Tatsuya Tada ◽

Shin Watanabe ◽

Mari Tohya ◽

Tomomi Hishinuma ◽

...

Keyword(s):

Public Health ◽

16S Rrna ◽

Enterobacter Cloacae ◽

Multidrug Resistant ◽

Epidemiological Surveillance ◽

New Delhi ◽

Content Type ◽

Carbapenem Resistant ◽

Genes Encoding ◽

Regional Public Health

ABSTRACT Surveillance of 10 hospitals and a regional public health laboratory in Myanmar identified 31 isolates of carbapenem-resistant Enterobacter cloacae complex harboring blaNDM-type. Of these isolates, 19 were highly resistant to aminoglycosides and harbored one or more genes encoding 16S rRNA methylases, including armA, rmtB, rmtC, and/or rmtE. Of the 19 isolates, 16 were Enterobacter xiangfangensis ST200, with armA on the chromosome and a plasmid harboring blaNDM-1 and rmtC, indicating that these isolates were clonally disseminated nationwide in Myanmar. IMPORTANCE The emergence of multidrug-resistant E. cloacae complex has become a public health threat worldwide. E. xiangfangensis is a recently classified species belonging to E. cloacae complex. Here, we report a clonal dissemination of multidrug-resistant E. xiangfangensis ST200 producing two types of New Delhi metallo-β-lactamase (NDM-type MBL), NDM-1 and -4, and three types of 16S rRNA methylases, ArmA, RmtC, and RmtE, in hospitals in Myanmar. The observation of these multidrug-resistant E. xiangfangensis ST200 isolates stresses the urgency to continue molecular epidemiological surveillance of these pathogens in Myanmar and in South Asian countries.

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Systematic Comparison of Epidemic and Non-Epidemic Carbapenem Resistant Klebsiella pneumoniae Strains

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.599924 ◽

2021 ◽

Vol 11 ◽

Author(s):

Katariina Koskinen ◽

Reetta Penttinen ◽

Anni-Maria Örmälä-Odegrip ◽

Christian G. Giske ◽

Tarmo Ketola ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Phenotypic Characteristics ◽

The Past ◽

Carbapenem Resistant ◽

Resistant Strains ◽

Preliminary Study ◽

Potential Factors ◽

Resource Levels ◽

Sequence Types

Over the past few decades, extensively drug resistant (XDR) resistant Klebsiella pneumoniae has become a notable burden to healthcare all over the world. Especially carbapenemase-producing strains are problematic due to their capability to withstand even last resort antibiotics. Some sequence types (STs) of K. pneumoniae are significantly more prevalent in hospital settings in comparison to other equally resistant strains. This provokes the question whether or not there are phenotypic characteristics that may render certain K. pneumoniae more suitable for epidemic dispersal between patients, hospitals, and different environments. In this study, we selected seven epidemic and non-epidemic carbapenem resistant K. pneumoniae isolates for extensive systematic characterization for phenotypic and genotypic qualities in order to identify potential factors that precede or emerge from epidemic successfulness. Studied characteristics include growth rates and densities in different conditions (media, temperature, pH, resource levels), tolerance to alcohol and drought, inhibition between strains, ability to compensate pH, as well as various genomic features. Overall, there are clear differences between isolates, yet, only drought tolerance was found to notably associate with non-epidemic K. pneumoniae strains. We further report a preliminary study on the potential to control K. pneumoniae ST11 with an antimicrobial component produced by a non-epidemic K. pneumoniae. This component initially restricts bacterial growth, but stable resistance develops rapidly in vitro.

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Characterization of a New Metallo-β-Lactamase Gene, blaNDM-1, and a Novel Erythromycin Esterase Gene Carried on a Unique Genetic Structure in Klebsiella pneumoniae Sequence Type 14 from India

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00774-09 ◽

2009 ◽

Vol 53 (12) ◽

pp. 5046-5054 ◽

Cited By ~ 1317

Author(s):

Dongeun Yong ◽

Mark A. Toleman ◽

Christian G. Giske ◽

Hyun S. Cho ◽

Kristina Sundman ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Sequence Type ◽

New Delhi ◽

Class 1 Integron ◽

Carbapenem Resistant ◽

Indian Origin ◽

Class 1 ◽

Esterase Gene ◽

Lactamase Gene

ABSTRACT A Swedish patient of Indian origin traveled to New Delhi, India, and acquired a urinary tract infection caused by a carbapenem-resistant Klebsiella pneumoniae strain that typed to the sequence type 14 complex. The isolate, Klebsiella pneumoniae 05-506, was shown to possess a metallo-β-lactamase (MBL) but was negative for previously known MBL genes. Gene libraries and amplification of class 1 integrons revealed three resistance-conferring regions; the first contained bla CMY-4 flanked by ISEcP1 and blc. The second region of 4.8 kb contained a complex class 1 integron with the gene cassettes arr-2, a new erythromycin esterase gene; ereC; aadA1; and cmlA7. An intact ISCR1 element was shown to be downstream from the qac/sul genes. The third region consisted of a new MBL gene, designated bla NDM-1, flanked on one side by K. pneumoniae DNA and a truncated IS26 element on its other side. The last two regions lie adjacent to one another, and all three regions are found on a 180-kb region that is easily transferable to recipient strains and that confers resistance to all antibiotics except fluoroquinolones and colistin. NDM-1 shares very little identity with other MBLs, with the most similar MBLs being VIM-1/VIM-2, with which it has only 32.4% identity. As well as possessing unique residues near the active site, NDM-1 also has an additional insert between positions 162 and 166 not present in other MBLs. NDM-1 has a molecular mass of 28 kDa, is monomeric, and can hydrolyze all β-lactams except aztreonam. Compared to VIM-2, NDM-1 displays tighter binding to most cephalosporins, in particular, cefuroxime, cefotaxime, and cephalothin (cefalotin), and also to the penicillins. NDM-1 does not bind to the carbapenems as tightly as IMP-1 or VIM-2 and turns over the carbapenems at a rate similar to that of VIM-2. In addition to K. pneumoniae 05-506, bla NDM-1 was found on a 140-kb plasmid in an Escherichia coli strain isolated from the patient's feces, inferring the possibility of in vivo conjugation. The broad resistance carried on these plasmids is a further worrying development for India, which already has high levels of antibiotic resistance.

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In Vivo Pharmacodynamics of β-Lactams/Nacubactam against Carbapenem-Resistant and/or Carbapenemase-Producing Enterobacter cloacae and Klebsiella pneumoniae in Murine Pneumonia Model

Antibiotics ◽

10.3390/antibiotics10101179 ◽

2021 ◽

Vol 10 (10) ◽

pp. 1179

Author(s):

Mao Hagihara ◽

Hideo Kato ◽

Toshie Sugano ◽

Hayato Okade ◽

Nobuo Sato ◽

...

Keyword(s):

Antimicrobial Activity ◽

Klebsiella Pneumoniae ◽

Treatment Options ◽

Enterobacter Cloacae ◽

Antimicrobial Activities ◽

Combination Therapies ◽

Carbapenem Resistant ◽

Combination Regimens

Carbapenem-resistant Enterobacterales (CRE) and carbapenemase-producing Enterobacterales (CPE) have become global threats. CRE− and CPE− derived infections have been associated with high mortality due to limited treatment options. Nacubactam is a β-lactamase inhibitor and belongs to the new class of diazabicyclooctane. The agent has an in vitro antimicrobial activity against several classes of β-lactamase-producing Enterobacterales. This study evaluated antimicrobial activity of combination therapies including β-lactams (aztreonam, cefepime, and meropenem) and nacubactam against four Enterobacter cloacae and six Klebsiella pneumoniae isolates with murine pneumonia model. Based on changes in bacterial quantity, antimicrobial activities of some regimens were assessed. Combination therapies including β-lactams (aztreonam, cefepime, and meropenem) with nacubactam showed enhanced antimicrobial activity against CRE E. cloacae (−3.70 to −2.08 Δlog10 CFU/lungs) and K. pneumoniae (−4.24 to 1.47 Δlog10 CFU/lungs) with IMP-1, IMP-6, or KPC genes, compared with aztreonam, cefepime, meropenem, and nacubactam monotherapies. Most combination therapies showed bacteriostatic (−3.0 to 0 Δlog10 CFU/lungs) to bactericidal (<−3.0 Δlog10 CFU/lungs) activities against CRE isolates. This study revealed that combination regimens with β-lactams (aztreonam, cefepime, and meropenem) and nacubactam are preferable candidates to treat pneumonia due to CRE and CPE.

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Klebsiella pneumoniae with capsule type K64 is overrepresented among invasive disease in Vietnam

F1000Research ◽

10.12688/f1000research.52799.1 ◽

2021 ◽

Vol 10 ◽

pp. 454

Author(s):

Bich Vu Thi Ngoc ◽

Sylvain Brisse ◽

Trinh Dao Tuyet ◽

Dung Vu Tien Viet ◽

Kathryn E Holt ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Susceptibility Testing ◽

Invasive Disease ◽

Community Acquired Pneumonia ◽

Capsule Type ◽

Carbapenem Resistant ◽

Rural And Urban ◽

Significant Difference ◽

Invasive Infections ◽

Sequence Types

Introduction: Recent reports indicate the emergence of community-acquired pneumonia associated with K64-Klebsiella pneumoniae. Here, we identify the capsular types and sequence type of invasive and commensal K. pneumoniae isolates from Vietnam. Methods: We included 93 K. pneumoniae isolates from patients hospitalized at the National Hospital for Tropical Diseases, Hanoi between 2007 and 2011; and 110 commensal isolates from throat swabs from healthy volunteers living in rural and urban Hanoi in 2012. We determined sequence types (STs) by multi-locus sequence typing (MLST) and capsule typing for seven K types by PCR. Antibiotic susceptibility testing was performed using disk diffusion. Results: The most common detected capsule types were K1 (39/203, 19.2%, mainly ST23) and K2 (31/203, 15.3%, multiple STs: ST65, ST86, ST380). We found significantly more K2 isolates among invasive in comparison to commensal isolates (22.6% vs 9%, p = 0.01) but no significant difference was observed between invasive and commensal K1 isolates (14.5% vs 24.7%, p = 0.075). K64 with varying sequence types were predominantly seen among invasive K. pneumoniae (8 vs. 3) and were isolated from sepsis and meningitis patients. Among K64 isolates, one was carbapenem-resistant with ST799. Conclusion: Our study confirms that capsule type K64 K. pneumoniae is associated with community-acquired invasive infections in Vietnam. Research is needed to unravel the mechanisms of virulence of capsule type K64 in both community and hospital settings.

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Emergence of Hybrid Resistance and Virulence Plasmids Harboring New Delhi Metallo-β-Lactamase in Klebsiella pneumoniae in Russia

Antibiotics ◽

10.3390/antibiotics10060691 ◽

2021 ◽

Vol 10 (6) ◽

pp. 691

Author(s):

Polina Starkova ◽

Irina Lazareva ◽

Alisa Avdeeva ◽

Ofeliia Sulian ◽

Darya Likholetova ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Resistance Genes ◽

New Delhi ◽

Actual Distribution ◽

High Identity ◽

Virulence Plasmids ◽

Carbapenem Resistant ◽

The Uk ◽

Sequence Types ◽

Two Hybrid

The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) is a new threat to healthcare. In this study, we analyzed nine CR-hvKp isolates of different sequence-types (ST) recovered from patients with nosocomial infections in two hospitals in Saint Petersburg. Whole-genome sequencing showed that eight of them harbored large mosaic plasmids carrying resistance to carbapenems and hypervirulence simultaneously, and four different types of hybrid plasmids were identified. BLAST analysis showed a high identity with two hybrid plasmids originating in the UK and Czech Republic. We demonstrated that hybrid plasmids emerged due to the acquisition of resistance genes by virulent plasmids. Moreover, one of the hybrid plasmids carried a novel New Delhi metallo-beta-lactamase (NDM) variant, differing from NDM-1 by one amino acid substitution (D130N), which did not provide significant evolutionary advantages compared to NDM-1. The discovery of structurally similar plasmids in geographically distant regions suggests that the actual distribution of hybrid plasmids carrying virulence and resistance genes is much wider than expected.

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