scholarly journals KPC-Producing, Multidrug-Resistant Klebsiella pneumoniae Sequence Type 258 as a Typical Opportunistic Pathogen

2013 ◽  
Vol 57 (10) ◽  
pp. 5144-5146 ◽  
Author(s):  
L. S. Tzouvelekis ◽  
V. Miriagou ◽  
S. D. Kotsakis ◽  
K. Spyridopoulou ◽  
E. Athanasiou ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Lethal Dose ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Antimicrobial Treatment ◽  
Sequence Type ◽  
Content Type ◽  
Serum Killing

ABSTRACTThe virulence of a KPC-producingKlebsiella pneumoniaesequence type 258 (ST258) strain representing those circulating in Greece was assessed in a mouse septicemia model. The strain was virtually avirulent (50% lethal dose, >108and 5 × 107CFU for immunocompetent and neutropenic animals, respectively). Also, it was highly susceptible to serum killing, rapidly phagocytosedin vitro, and classified as K41, which is not among the virulent capsular types. The findings indirectly support the notion that high ST258-associated mortality is largely due to inefficient antimicrobial treatment.

scholarly journals Doripenem MICs andompK36Porin Genotypes of Sequence Type 258, KPC-Producing Klebsiella pneumoniae May Predict Responses to Carbapenem-Colistin Combination Therapy among Patients with Bacteremia

2014 ◽  
Vol 59 (3) ◽  
pp. 1797-1801 ◽  
Author(s):  
Ryan K. Shields ◽  
M. Hong Nguyen ◽  
Brian A. Potoski ◽  
Ellen G. Press ◽  
Liang Chen ◽  
...  
Keyword(s):  
Amino Acids ◽  
Combination Therapy ◽  
Klebsiella Pneumoniae ◽  
Sequence Type ◽  
Content Type

ABSTRACTTreatment failures of a carbapenem-colistin regimen among patients with bacteremia due to sequence type 258 (ST258), KPC-2-producingKlebsiella pneumoniaewere significantly more likely if both agents were inactivein vitro, as defined by a colistin MIC of >2 μg/ml and the presence of either a majorompK36porin mutation (guanine and alanine insertions at amino acids 134 and 135 [ins aa 134–135 GD], IS5promoter insertion [P= 0.007]) or a doripenem MIC of >8 μg/ml (P= 0.01). MajorompK36mutations among KPC-K. pneumoniaestrains are important determinants of carbapenem-colistin responsesin vitroandin vivo.

scholarly journals Avibactam Restores the Susceptibility of Clinical Isolates of Stenotrophomonas maltophilia to Aztreonam

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Maria F. Mojica ◽  
Krisztina M. Papp-Wallace ◽  
Magdalena A. Taracila ◽  
Melissa D. Barnes ◽  
Joseph D. Rutter ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
World Health ◽  
Combination Therapies ◽  
Content Type ◽  
Medical Need ◽  
The World ◽  
Health Organization

ABSTRACT Stenotrophomonas maltophilia is an emerging opportunistic pathogen, classified by the World Health Organization as one of the leading multidrug-resistant organisms in hospital settings. The need to discover novel compounds and/or combination therapies for S. maltophilia is urgent. We demonstrate the in vitro efficacy of aztreonam-avibactam (ATM-AVI) against S. maltophilia and kinetically characterize the inhibition of the L2 β-lactamase by avibactam. ATM-AVI overcomes aztreonam resistance in selected clinical strains of S. maltophilia, addressing an unmet medical need.

scholarly journals Carbapenem-Resistant Klebsiella pneumoniae Strains Exhibit Diversity in Aminoglycoside-Modifying Enzymes, Which Exert Differing Effects on Plazomicin and Other Agents

2014 ◽  
Vol 58 (8) ◽  
pp. 4443-4451 ◽  
Author(s):  
Reem Almaghrabi ◽  
Cornelius J. Clancy ◽  
Yohei Doi ◽  
Binghua Hao ◽  
Liang Chen ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Bactericidal Activity ◽  
Sequence Type ◽  
Content Type ◽  
Molecular Assays ◽  
Carbapenem Resistant ◽  
Research Priority ◽  
Gentamicin Resistance

ABSTRACTWe measuredin vitroactivity of plazomicin, a next-generation aminoglycoside, and other aminoglycosides against 50 carbapenem-resistantKlebsiella pneumoniaestrains from two centers and correlated the results with the presence of various aminoglycoside-modifying enzymes (AMEs). Ninety-four percent of strains were sequence type 258 (ST258) clones, which exhibited 5ompK36genotypes; 80% and 10% of strains producedKlebsiella pneumoniaecarbapenemase 2 (KPC-2) and KPC-3, respectively. Ninety-eight percent of strains possessed AMEs, including AAC(6′)-Ib (98%), APH(3′)-Ia (56%), AAC(3)-IV (38%), and ANT(2″)-Ia (2%). Gentamicin, tobramycin, and amikacin nonsusceptibility rates were 40, 98, and 16%, respectively. Plazomicin MICs ranged from 0.25 to 1 μg/ml. Tobramycin and plazomicin MICs correlated with gentamicin MICs (r= 0.75 and 0.57, respectively). Plazomicin exerted bactericidal activity against 17% (1× MIC) and 94% (4× MIC) of strains. All strains with AAC(6′)-Ib were tobramycin-resistant; 16% were nonsusceptible to amikacin. AAC(6′)-Ib combined with another AME was associated with higher gentamicin, tobramycin, and plazomicin MICs than AAC(6′)-Ib alone (P= 0.01, 0.0008, and 0.046, respectively). The presence of AAC(3)-IV in a strain was also associated with higher gentamicin, tobramycin, and plazomicin MICs (P= 0.0006,P< 0.0001, andP= 0.01, respectively). The combination of AAC(6′)-Ib and another AME, the presence of AAC(3)-IV, and the presence of APH(3′)-Ia were each associated with gentamicin resistance (P= 0.0002, 0.003, and 0.01, respectively). In conclusion, carbapenem-resistantK. pneumoniaestrains (including ST258 clones) exhibit highly diverse antimicrobial resistance genotypes and phenotypes. Plazomicin may offer a treatment option against strains resistant to other aminoglycosides. The development of molecular assays that predict antimicrobial responses among carbapenem-resistantK. pneumoniaestrains should be a research priority.

scholarly journals Emergence of a Multidrug-Resistant Hypervirulent Klebsiella pneumoniae Sequence Type 23 Strain with a Rare blaCTX-M-24-Harboring Virulence Plasmid

2019 ◽  
Vol 63 (3) ◽  
Author(s):  
Dingxia Shen ◽  
Guannan Ma ◽  
Cuidan Li ◽  
Xinmiao Jia ◽  
Chuan Qin ◽  
...  
Keyword(s):  
Public Health ◽  
Klebsiella Pneumoniae ◽  
Genetic Basis ◽  
Virulence Genes ◽  
Multidrug Resistant ◽  
Sequence Type ◽  
Hybrid Plasmid ◽  
Virulence Plasmid ◽  
Drug Resistant ◽  
Content Type

ABSTRACT Here, we report a multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-HvKP) strain of sequence type 23 (ST23) with a rare hybrid plasmid harboring virulence genes and blaCTX-M-24, and we analyze the genetic basis for relationship between genotypes and MDR-hypervirulence phenotypes. Further analysis indicates that the hybrid plasmid is formed by IS903D-mediated intermolecular transposition of the blaCTX-M-24 gene into the virulence plasmid. The emergence of MDR-HvKP strains, especially those carrying drug-resistant virulent plasmids, poses unprecedented threats/challenges to public health. This is a dangerous trend and should be closely monitored.

scholarly journals Colistin Resistance Gene mcr-8 in a High-Risk Sequence Type 15 Klebsiella pneumoniae Isolate from Kenya

2020 ◽  
Vol 9 (39) ◽  
Author(s):  
Cecilia Kyany’a ◽  
Lillian Musila
Keyword(s):  
High Risk ◽  
Klebsiella Pneumoniae ◽  
Resistance Gene ◽  
Resistance Genes ◽  
Multidrug Resistant ◽  
Sequence Type ◽  
Colistin Resistance ◽  
Content Type ◽  
Global Concern ◽  
Hospitalized Patient

ABSTRACT The emergence and rise of mobile colistin resistance genes are of great global concern due to the ease of transfer of resistance to other bacteria. This report describes the genome of a colistin- and multidrug-resistant Klebsiella pneumoniae isolate bearing mcr-8, obtained from a hospitalized patient in Kenya.

scholarly journals In Vitro Discordance with In Vivo Activity: Humanized Exposures of Ceftazidime-Avibactam, Aztreonam, and Tigecycline Alone and in Combination against New Delhi Metallo-β-Lactamase-Producing Klebsiella pneumoniae in a Murine Lung Infection Model

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
M. L. Monogue ◽  
L. M. Abbo ◽  
R. Rosa ◽  
J. F. Camargo ◽  
O. Martinez ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Lung Infection ◽  
Multidrug Resistant ◽  
Infection Model ◽  
New Delhi ◽  
Beta Lactamase ◽  
Bacterial Reduction ◽  
Content Type

ABSTRACT The management of infections with New Delhi metallo-beta-lactamase-1 (NDM)-producing bacteria remains clinically challenging given the multidrug resistant (MDR) phenotype associated with these bacteria. Despite resistance in vitro, ceftazidime-avibactam previously demonstrated in vivo activity against NDM-positive Enterobacteriaceae. Herein, we observed in vitro synergy with ceftazidime-avibactam and aztreonam against an MDR Klebsiella pneumoniae harboring NDM. In vivo, humanized doses of ceftazidime-avibactam monotherapy resulted in >2 log10 CFU bacterial reduction; therefore, no in vivo synergy was observed.

scholarly journals Klebsiella pneumoniae Sequence Type 11 from Companion Animals Bearing ArmA Methyltransferase, DHA-1 β-Lactamase, and QnrB4

2013 ◽  
Vol 57 (9) ◽  
pp. 4532-4534 ◽  
Author(s):  
Laura Hidalgo ◽  
Belen Gutierrez ◽  
Cristina M. Ovejero ◽  
Laura Carrilero ◽  
Stephanie Matrat ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multilocus Sequence Typing ◽  
Companion Animals ◽  
Multidrug Resistant ◽  
Sequence Type ◽  
Resistance Determinant ◽  
Epidemic Clone ◽  
Content Type ◽  
First Report

ABSTRACTSevenKlebsiella pneumoniaeisolates from dogs and cats in Spain were found to be highly resistant to aminoglycosides, and ArmA methyltransferase was responsible for this phenotype. All isolates were typed by multilocus sequence typing (MLST) as ST11, a human epidemic clone reported worldwide and associated with, among others, OXA-48 and NDM carbapenemases. In the seven strains,armAwas borne by an IncR plasmid, pB1025, of 50 kb. The isolates were found to coproduce DHA-1 and SHV-11 β-lactamases, as well as the QnrB4 resistance determinant. This first report of the ArmA methyltransferase in pets illustrates their importance as a reservoir for human multidrug-resistantK. pneumoniae.

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

2014 ◽  
Vol 59 (2) ◽  
pp. 1038-1047 ◽  
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.

scholarly journals Mutations of theompK36Porin Gene and Promoter Impact Responses of Sequence Type 258, KPC-2-Producing Klebsiella pneumoniae Strains to Doripenem and Doripenem-Colistin

2013 ◽  
Vol 57 (11) ◽  
pp. 5258-5265 ◽  
Author(s):  
Cornelius J. Clancy ◽  
Liang Chen ◽  
Jae H. Hong ◽  
Shaoji Cheng ◽  
Binghua Hao ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Amino Acid ◽  
Klebsiella Pneumoniae ◽  
Independent Predictor ◽  
Gene Mutations ◽  
Sequence Type ◽  
Wild Type ◽  
Content Type ◽  
Time Kill

ABSTRACTDoripenem-colistin exerts synergy against some, but not all,Klebsiella pneumoniaecarbapenemase (KPC)-producingK. pneumoniaestrainsin vitro. We determined if doripenem MICs and/orompK36porin gene mutations impacted the responses of 23 sequence type 258 (ST258), KPC-2-producing strains to the combination of doripenem (8 μg/ml) and colistin (2 μg/ml) during time-kill assays. The median doripenem and colistin MICs were 32 and 4 μg/ml. Doripenem MICs did not correlate with KPC-2 expression levels. Five and 18 strains had wild-type and mutantompK36, respectively. The most common mutations were IS5promoter insertions (n= 7) and insertions encoding glycine and aspartic acid at amino acid (aa) positions 134 and 135 (ins aa134-135 GD;n= 8), which were associated with higher doripenem MICs than other mutations or wild-typeompK36(allPvalues ≤ 0.04). Bactericidal activity (24 h) was achieved by doripenem-colistin against 12%, 43%, and 75% of ins aa134-135 GD, IS5, and wild-type/other mutants, respectively (P= 0.04). Doripenem-colistin was more active in time-kill studies than colistin at 12 and 24 h if the doripenem MIC was ≤8 μg/ml (P= 0.0007 and 0.09, respectively), but not if the MIC was >8 μg/ml (P= 0.10 and 0.16). Likewise, doripenem-colistin was more active at 12 and 24 h against the wild type/other mutants than ins aa134-135 GD or IS5mutants (P= 0.007 and 0.0007). By multivariate analysis, the absence of ins aa134-135 GD or IS5mutations was the only independent predictor of doripenem-colistin responses at 24 h (P= 0.002). In conclusion,ompK36genotypes identified ST258 KPC-K. pneumoniaestrains that were most likely to respond to doripenem-colistin.

scholarly journals In Vitro and In Vivo Activities of β-Lactams in Combination with the Novel β-Lactam Enhancers Zidebactam and WCK 5153 against Multidrug-Resistant Metallo-β-Lactamase-Producing Klebsiella pneumoniae

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Bartolome Moya ◽  
Isabel M. Barcelo ◽  
Gabriel Cabot ◽  
Gabriel Torrens ◽  
Snehal Palwe ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Molecular Targets ◽  
Multidrug Resistant ◽  
The Novel ◽  
Penicillin Binding Protein ◽  
Content Type ◽  
Time Kill

ABSTRACT Zidebactam and WCK 5153 are novel bicyclo-acyl hydrazide (BCH) agents that have previously been shown to act as β-lactam enhancer (BLE) antibiotics in Pseudomonas aeruginosa and Acinetobacter baumannii. The objectives of this work were to identify the molecular targets of these BCHs in Klebsiella pneumoniae and to investigate their potential BLE activity for cefepime and aztreonam against metallo-β-lactamase (MBL)-producing strains in vitro and in vivo. Penicillin binding protein (PBP) binding profiles were determined by Bocillin FL assay, and 50% inhibitory concentrations (IC50s) were determined using ImageQuant TL software. MICs and kill kinetics for zidebactam, WCK 5153, and cefepime or aztreonam, alone and in combination, were determined against clinical K. pneumoniae isolates producing MBLs VIM-1 or NDM-1 (plus ESBLs and class C β-lactamases) to assess the in vitro enhancer effect of BCH compounds in conjunction with β-lactams. Additionally, murine systemic and thigh infection studies were conducted to evaluate BLE effects in vivo. Zidebactam and WCK 5153 showed specific, high PBP2 affinity in K. pneumoniae. The MICs of BLEs were >64 μg/ml for all MBL-producing strains. Time-kill studies showed that a combination of these BLEs with either cefepime or aztreonam provided 1 to >3 log10 kill against MBL-producing K. pneumoniae strains. Furthermore, the bactericidal synergy observed for these BLE–β-lactam combinations translated well into in vivo efficacy even in the absence of MBL inhibition by BLEs, a characteristic feature of the β-lactam enhancer mechanism of action. Zidebactam and WCK 5153 are potent PBP2 inhibitors and display in vitro and in vivo BLE effects against multidrug-resistant (MDR) K. pneumoniae clinical isolates producing MBLs.

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