scholarly journals ARGONAUT II Study of the In Vitro Activity of Plazomicin against Carbapenemase-Producing Klebsiella pneumoniae

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Michael R. Jacobs ◽  
Caryn E. Good ◽  
Andrea M. Hujer ◽  
Ayman M. Abdelhamed ◽  
Daniel D. Rhoads ◽  
...  
Keyword(s):  
United States ◽  
16S Rrna ◽  
Klebsiella Pneumoniae ◽  
Great Lakes ◽  
The United States ◽  
Great Lakes Region ◽  
In Vitro Activity ◽  
Content Type ◽  
Carbapenem Resistant

ABSTRACT Plazomicin was tested against 697 recently acquired carbapenem-resistant Klebsiella pneumoniae isolates from the Great Lakes region of the United States. Plazomicin MIC50 and MIC90 values were 0.25 and 1 mg/liter, respectively; 680 isolates (97.6%) were susceptible (MICs of ≤2 mg/liter), 9 (1.3%) intermediate (MICs of 4 mg/liter), and 8 (1.1%) resistant (MICs of >32 mg/liter). Resistance was associated with rmtF-, rmtB-, or armA-encoded 16S rRNA methyltransferases in all except 1 isolate.

scholarly journals Colistin Heteroresistance Is Largely Undetected among Carbapenem-Resistant Enterobacterales in the United States

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Victor I. Band ◽  
Sarah W. Satola ◽  
Richard D. Smith ◽  
David A. Hufnagel ◽  
Chris Bower ◽  
...  
Keyword(s):  
United States ◽  
Klebsiella Pneumoniae ◽  
Diagnostic Testing ◽  
Cladistic Analysis ◽  
The United States ◽  
Clinical Diagnostics ◽  
Infection Model ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Clinical Diagnostic

ABSTRACT Heteroresistance is a form of antibiotic resistance where a bacterial strain is comprised of a minor resistant subpopulation and a majority susceptible subpopulation. We showed previously that colistin heteroresistance can mediate the failure of colistin therapy in an in vivo infection model, even for isolates designated susceptible by clinical diagnostics. We sought to characterize the extent of colistin heteroresistance among the highly drug-resistant carbapenem-resistant Enterobacterales (CRE). We screened 408 isolates for colistin heteroresistance. These isolates were collected between 2012 and 2015 in eight U.S. states as part of active surveillance for CRE. Colistin heteroresistance was detected in 10.1% (41/408) of isolates, and it was more common than conventional homogenous resistance (7.1%, 29/408). Most (93.2%, 38/41) of these heteroresistant isolates were classified as colistin susceptible by standard clinical diagnostic testing. The frequency of colistin heteroresistance was greatest in 2015, the last year of the study. This was especially true among Enterobacter isolates, of which specific species had the highest rates of heteroresistance. Among Klebsiella pneumoniae isolates, which were the majority of isolates tested, there was a closely related cluster of colistin-heteroresistant ST-258 isolates found mostly in Georgia. However, cladistic analysis revealed that, overall, there was significant diversity in the genetic backgrounds of heteroresistant K. pneumoniae isolates. These findings suggest that due to being largely undetected in the clinic, colistin heteroresistance among CRE is underappreciated in the United States. IMPORTANCE Heteroresistance is an underappreciated phenomenon that may be the cause of some unexplained antibiotic treatment failures. Misclassification of heteroresistant isolates as susceptible may lead to inappropriate therapy. Heteroresistance to colistin was more common than conventional resistance and was overwhelmingly misclassified as susceptibility by clinical diagnostic testing. Higher proportions of colistin heteroresistance observed in certain Enterobacter species and clustering among heteroresistant Klebsiella pneumoniae strains may inform colistin treatment recommendations. Overall, the rate of colistin nonsusceptibility was more than double the level detected by clinical diagnostics, suggesting that the prevalence of colistin nonsusceptibility among CRE may be higher than currently appreciated in the United States.

scholarly journals Global Dissemination ofblaKPCinto Bacterial Species beyond Klebsiella pneumoniae andIn VitroSusceptibility to Ceftazidime-Avibactam and Aztreonam-Avibactam

2016 ◽  
Vol 60 (8) ◽  
pp. 4490-4500 ◽  
Author(s):  
Krystyna M. Kazmierczak ◽  
Douglas J. Biedenbach ◽  
Meredith Hackel ◽  
Sharon Rabine ◽  
Boudewijn L. M. de Jonge ◽  
...  
Keyword(s):  
United States ◽  
Klebsiella Pneumoniae ◽  
Molecular Mechanisms ◽  
Bacterial Species ◽  
The United States ◽  
Asia Pacific ◽  
Gram Negative ◽  
Content Type ◽  
Global Problem

ABSTRACTTheKlebsiella pneumoniaecarbapenemase (KPC), first described in the United States in 1996, is now a widespread global problem in several Gram-negative species. A worldwide surveillance study collected Gram-negative pathogens from 202 global sites in 40 countries during 2012 to 2014 and determined susceptibility to β-lactams and other class agents by broth microdilution testing. Molecular mechanisms of β-lactam resistance among carbapenem-nonsusceptibleEnterobacteriaceaeandPseudomonas aeruginosawere determined using PCR and sequencing. Genes encoding KPC enzymes were found in 586 isolates from 22 countries (76 medical centers), including countries in the Asia-Pacific region (32 isolates), Europe (264 isolates), Latin America (210 isolates), and the Middle East (19 isolates, Israel only) and the United States (61 isolates). The majority of isolates wereK. pneumoniae(83.4%); however, KPC was detected in 13 additional species. KPC-2 (69.6%) was more common than KPC-3 (29.5%), with regional variation observed. A novel KPC variant, KPC-18 (KPC-3[V8I]), was identified during the study. Few antimicrobial agents tested remained effectivein vitroagainst KPC-producing isolates, with ceftazidime-avibactam (MIC90, 4 μg/ml), aztreonam-avibactam (MIC90, 0.5 μg/ml), and tigecycline (MIC90, 2 μg/ml) retaining the greatest activity againstEnterobacteriaceaecocarrying KPC and other β-lactamases, whereas colistin (MIC90, 2 μg/ml) demonstrated the greatestin vitroactivity against KPC-positiveP. aeruginosa. This analysis of surveillance data demonstrated that KPC is widely disseminated. KPC was found in multiple species ofEnterobacteriaceaeandP. aeruginosaand has now become a global problem.

scholarly journals Characterization of a Novel Hepadnavirus in the White Sucker (Catostomus commersonii) from the Great Lakes Region of the United States

2015 ◽  
Vol 89 (23) ◽  
pp. 11801-11811 ◽  
Author(s):  
Cassidy M. Hahn ◽  
Luke R. Iwanowicz ◽  
Robert S. Cornman ◽  
Carla M. Conway ◽  
James R. Winton ◽  
...  
Keyword(s):  
United States ◽  
Hepatitis B ◽  
Great Lakes ◽  
Amino Acid Level ◽  
The United States ◽  
Great Lakes Region ◽  
Hepatic Tumors ◽  
White Sucker ◽  
Novel Genus ◽  
Content Type

ABSTRACTThe white suckerCatostomus commersoniiis a freshwater teleost often utilized as a resident sentinel. Here, we sequenced the full genome of a hepatitis B-like virus that infects white suckers from the Great Lakes Region of the United States. Dideoxy sequencing confirmed that the white sucker hepatitis B virus (WSHBV) has a circular genome (3,542 bp) with the prototypical codon organization of hepadnaviruses. Electron microscopy demonstrated that complete virions of approximately 40 nm were present in the plasma of infected fish. Compared to avi- and orthohepadnaviruses, sequence conservation of the core, polymerase, and surface proteins was low and ranged from 16 to 27% at the amino acid level. An X protein homologue common to the orthohepadnaviruses was not present. The WSHBV genome included an atypical, presumptively noncoding region absent in previously described hepadnaviruses. Phylogenetic analyses confirmed WSHBV as distinct from previously documented hepadnaviruses. The level of divergence in protein sequences between WSHBV and other hepadnaviruses and the identification of an HBV-like sequence in an African cichlid provide evidence that a novel genus of the familyHepadnaviridaemay need to be established that includes these hepatitis B-like viruses in fishes. Viral transcription was observed in 9.5% (16 of 169) of white suckers evaluated. The prevalence of hepatic tumors in these fish was 4.9%, and only 2.4% of fish were positive for both virus and hepatic tumors. These results are not sufficient to draw inferences regarding the association of WSHBV and carcinogenesis in white sucker.IMPORTANCEWe report the first full-length genome of a hepadnavirus from fishes. Phylogenetic analysis of this genome indicates divergence from genomes of previously described hepadnaviruses from mammalian and avian hosts and supports the creation of a novel genus. The discovery of this novel virus may better our understanding of the evolutionary history of hepatitis B-like viruses of other hosts. In fishes, knowledge of this virus may provide insight regarding possible risk factors associated with hepatic neoplasia in the white sucker. This may also offer another model system for mechanistic research.

scholarly journals In Vitro Activity of Imipenem-Relebactam against Gram-Negative ESKAPE Pathogens Isolated by Clinical Laboratories in the United States in 2015 (Results from the SMART Global Surveillance Program)

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Sibylle H. Lob ◽  
Meredith A. Hackel ◽  
Krystyna M. Kazmierczak ◽  
Katherine Young ◽  
Mary R. Motyl ◽  
...  
Keyword(s):  
United States ◽  
Klebsiella Pneumoniae ◽  
Antimicrobial Agents ◽  
The United States ◽  
Surveillance Program ◽  
Gram Negative ◽  
Content Type ◽  
Clinical Laboratories ◽  
Eskape Pathogens

ABSTRACT Relebactam (formerly MK-7655) is an inhibitor of class A and C β-lactamases, including Klebsiella pneumoniae carbapenemase (KPC), and is currently in clinical development in combination with imipenem-cilastatin. Using Clinical and Laboratory Standards Institute (CLSI)-defined broth microdilution methodology, we evaluated the in vitro activities of imipenem-relebactam, imipenem, and seven routinely tested parenteral antimicrobial agents against Gram-negative ESKAPE pathogens (including Klebsiella pneumoniae, n = 689; Acinetobacter baumannii, n = 72; Pseudomonas aeruginosa, n = 845; and Enterobacter spp., n = 399) submitted by 21 clinical laboratories in the United States in 2015 as part of the SMART (Study for Monitoring Antimicrobial Resistance Trends) global surveillance program. Relebactam was tested at a fixed concentration of 4 μg/ml in combination with doubling dilutions of imipenem. Imipenem-relebactam MICs were interpreted using CLSI imipenem breakpoints. The respective rates of susceptibility to imipenem-relebactam and imipenem were 94.2% (796/845) and 70.3% (594/845) for P. aeruginosa, 99.0% (682/689) and 96.1% (662/689) for K. pneumoniae, and 100% (399/399) and 98.0% (391/399) for Enterobacter spp. Relebactam restored imipenem susceptibility to 80.5% (202/251), 74.1% (20/27), and 100% (8/8) of isolates of imipenem-nonsusceptible P. aeruginosa, K. pneumoniae, and Enterobacter spp. Relebactam did not increase the number of isolates of Acinetobacter spp. susceptible to imipenem, and the rates of resistance to all of the agents tested against this pathogen were >30%. Further development of imipenem-relebactam is warranted given the demonstrated ability of relebactam to restore the activity of imipenem against current clinical isolates of Enterobacteriaceae and P. aeruginosa that are nonsusceptible to carbapenems and its potential as a therapy for treating patients with antimicrobial-resistant Gram-negative infections.

scholarly journals Multiplex PCR Analysis for Rapid Detection of Klebsiella pneumoniae Carbapenem-Resistant (Sequence Type 258 [ST258] and ST11) and Hypervirulent (ST23, ST65, ST86, and ST375) Strains

2018 ◽  
Vol 56 (9) ◽  
Author(s):  
Fangyou Yu ◽  
Jingnan Lv ◽  
Siqiang Niu ◽  
Hong Du ◽  
Yi-Wei Tang ◽  
...  
Keyword(s):  
United States ◽  
Klebsiella Pneumoniae ◽  
Multiplex Pcr ◽  
Virulence Genes ◽  
The United States ◽  
Sequence Type ◽  
Pcr Assay ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Resistant Strains

ABSTRACT Carbapenem-resistant and hypervirulent Klebsiella pneumoniae strains have emerged recently. These strains are both hypervirulent and multidrug resistant and may also be highly transmissible and able to cause severe infections in both the hospital and the community. Clinical and public health needs require a rapid and comprehensive molecular detection assay to identify and track the spread of these strains and provide timely infection control information. Here, we develop a rapid multiplex PCR assay capable of distinguishing K. pneumoniae carbapenem-resistant isolates of sequence type 258 (ST258) and ST11, and hypervirulent ST23, ST65/ST375, and ST86 clones, as well as capsular types K1, K2, K locus type 47 (KL47), and KL64, and virulence genes rmpA, rmpA2, iutA, and iroN. The assay demonstrated 100% concordance with 118 previously genotyped K. pneumoniae isolates and revealed different populations of carbapenem-resistant and hypervirulent strains in two collections in China and the United States. The results showed that carbapenem-resistant and hypervirulent K. pneumoniae strains are still rare in the United States, whereas in China, ∼50% of carbapenem-resistant strains carry rmpA/rmpA2 and iutA virulence genes, which are largely associated with the epidemic ST11 strains. Similarly, a high prevalence of hypervirulent strains was found in carbapenem-susceptible isolates in two Chinese hospitals, but these primarily belong to ST23, ST65/ST375, and ST86, which are distinct from the carbapenem-resistant strains. Taken together, our results demonstrated that this PCR assay can be a useful tool for molecular surveillance of carbapenem-resistant and hypervirulent K. pneumoniae strains.

scholarly journals In Vitro Activity of Ceftazidime-Avibactam against Carbapenem-Resistant and Hypervirulent Klebsiella pneumoniae Isolates

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Fangyou Yu ◽  
Jingnan Lv ◽  
Siqiang Niu ◽  
Hong Du ◽  
Yi-Wei Tang ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clinical Experience ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Antimicrobial Treatment ◽  
In Vitro Activity ◽  
Content Type ◽  
Highly Active ◽  
Carbapenem Resistant

ABSTRACT Carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKp) strains have emerged while antimicrobial treatment options remain limited. Herein, we tested the in vitro activity of ceftazidime-avibactam and other comparator antibiotics against 65 CR-hvKp isolates. Ceftazidime-avibactam, colistin, and tigecycline are highly active in vitro against CR-hvKp isolates (MIC90, ≤1 μg/ml), including K. pneumoniae carbapenemase 2 (KPC-2)-producing ST11 CR-hvKp. On the basis of previous clinical experience and the in vitro data presented herein, we posit that ceftazidime-avibactam is a therapeutic option against CR-hvKp infections.

scholarly journals Antimicrobial Susceptibility among Pathogens Collected from Hospitalized Patients in the United States and In Vitro Activity of Tigecycline, a New Glycylcycline Antimicrobial

2006 ◽  
Vol 50 (10) ◽  
pp. 3479-3484 ◽  
Author(s):  
Ken B. Waites ◽  
Lynn B. Duffy ◽  
Michael J. Dowzicky
Keyword(s):  
United States ◽  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Klebsiella Pneumoniae ◽  
Klebsiella Oxytoca ◽  
Enterobacter Aerogenes ◽  
Enterobacter Cloacae ◽  
The United States ◽  
In Vitro Activity

ABSTRACT The activities of tigecycline and comparators against isolates collected from 76 U.S. centers between January 2004 and September 2005 were assessed. Tigecycline MIC90s were ≤2 μg/ml for Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae, Serratia marcescens, Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, and Streptococcus agalactiae.

Implications of the 2012 U.S. Election for U.S. Policy in Africa’s Great Lakes Region

2013 ◽  
Vol 56 (2) ◽  
pp. 185-191
Author(s):  
Georges Nzongola-Ntalaja
Keyword(s):  
United States ◽  
Natural Resources ◽  
Great Lakes ◽  
Democratic Republic ◽  
The United States ◽  
Great Lakes Region ◽  
Security Sector ◽  
White House ◽  
Republic Of The Congo ◽  
The U.S

Abstract:While Africans are generally satisfied that a person of African descent was reelected to the White House following a campaign in which vicious and racist attacks were made against him, the U.S. Africa policy under President Barack Obama will continue to be guided by the strategic interests of the United States, which are not necessarily compatible with the popular aspirations for democracy, peace, and prosperity in Africa. Obama’s policy in the Great Lakes region provides an excellent illustration of this point. Since Rwanda and Uganda are Washington’s allies in the “war against terror” in Darfur and Somalia, respectively, the Obama administration has done little to stop Kigali and Kampala from destabilizing the Democratic Republic of the Congo (DRC) and looting its natural resources, either directly or through proxies. Rwanda and Uganda have even been included in an international oversight mechanism that is supposed to guide governance and security sector reforms in the DRC, but whose real objective is to facilitate Western access to the enormous natural wealth of the Congo and the Great Lakes region.

scholarly journals Mycobacterium talmoniae, a Potential Pulmonary Pathogen Isolated from Multiple Patients with Bronchiectasis in the United States, Including the First Case of Clinical Disease in a Patient with Cystic Fibrosis

2018 ◽  
Vol 57 (2) ◽  
Author(s):  
Ravikiran Vasireddy ◽  
Sruthi Vasireddy ◽  
Barbara A. Brown-Elliott ◽  
Alexander L. Greninger ◽  
Rebecca M. Davidson ◽  
...  
Keyword(s):  
United States ◽  
Cystic Fibrosis ◽  
16S Rrna ◽  
Type Strain ◽  
Gene Sequencing ◽  
The United States ◽  
Average Nucleotide Identity ◽  
Content Type ◽  
First Case ◽  
Multiple Patients

ABSTRACTWe characterize three respiratory isolates of the recently described speciesMycobacterium talmoniaerecovered in Texas, Louisiana, and Massachusetts, including the first case of disease in a patient with underlying cystic fibrosis. The three isolates had a 100% match toM. talmoniaeNE-TNMC-100812Tby complete 16S rRNA,rpoBregion V, andhsp65 gene sequencing. Core genomic comparisons between one isolate and the type strain revealed an average nucleotide identity of 99.8%. The isolates were susceptible to clarithromycin, amikacin, and rifabutin, while resistance was observed for tetracyclines, ciprofloxacin, and linezolid.M. talmoniaeshould be added to the list of potential pulmonary pathogens, including in the setting of cystic fibrosis.

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