#Phenotypic, biochemical and #genetic analysis of #KPC-41, a KPC-3 variant conferring #resistance to #ceftazidime-avibactam and exhibiting reduced #carbapenemase activity (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Phenotypic, biochemical and genetic analysis of KPC-41, a KPC-3 variant conferring resistance to ceftazidime-avibactam and exhibiting reduced carbapenemase activity

Linda Mueller, Amandine Masseron, Guy Prod’Hom, Tatiana Galperine, Gilbert Greub, Laurent Poirel, Patrice Nordmann

DOI: 10.1128/AAC.01111-19

 

ABSTRACT

A novel KPC variant, KPC-41, was identified in a Klebsiella pneumoniae clinical isolate from Switzerland. This ß-lactamase possessed a three amino-acid insertion (Pro-Asn-Lys) located between amino acids 269 and 270 compared to the KPC-3 amino acid sequence. Cloning and expression of the blaKPC-41 gene in Escherichia coli, followed by determination of MIC values and kinetic parameters, showed that KPC-41, compared to KPC-3, has an increased affinity to ceftazidime and a decreased sensitivity to avibactam, leading to resistance to ceftazidime-avibactam once produced in K. pneumoniae. Furthermore, KPC-41 exhibited a drastic decrease of its carbapenemase activity. This report highlights that a diversity of KPC variants conferring resistance to ceftazidime-avibactam already circulate in Europe.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Klebsiella pneumoniae; Ceftazidime; Avibactam.

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Co- #Infections of Two #Strains of #NDM-1 and #OXA-232 Co-producing #Klebsiella pneumoniae in a #Kidney #Transplant Patient (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Co-Infections of Two Strains of NDM-1 and OXA-232 Co-producing Klebsiella pneumoniae in a Kidney Transplant Patient

Deisy A. Contreras, Sean P. Fitzwater, Deepa D. Nanayakkara, Joanna Schaenman, Grace M. Aldrovandi, Omai B. Garner, Shangxin Yang

DOI: 10.1128/AAC.00948-19

 

ABSTRACT

We report here a fatal case of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in a renal transplant patient without travel history in the past year, from whom 2 genetically different CRKP (ST14 and ST2497) strains carrying the same plasmids and anti-microbial resistance genes including blaNDM-1, blaOXA-232, blaCTX-M-15, armA and tet(D) were isolated from blood and abdominal cavity. The isolates were susceptible to colistin, tigecycline, eravacycline and cefiderocol, which was used to treat the CRKP in combination with ceftazidime/avibactam and polymyxin B and resulted in bacterial clearance. Despite the aggressive treatment, the patient died of ischemic colitis and multi-organ failure.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; NDM1; Carbapenem; Klebsiella pneumoniae.

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A promising bioconjugate #vaccine against hypervirulent #Klebsiella pneumoniae (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

A promising bioconjugate vaccine against hypervirulent Klebsiella pneumoniae

Mario F. Feldman, Anne E. Mayer Bridwell, Nichollas E. Scott, Evgeny Vinogradov, Samuel R. McKee, Sthefany M. Chavez, Joy Twentyman, Christina L. Stallings, David A. Rosen, and Christian M. Harding

PNAS first published August 27, 2019 / DOI: https://doi.org/10.1073/pnas.1907833116

Edited by Dennis L. Kasper, Harvard Medical School, Boston, MA, and approved August 6, 2019 (received for review May 6, 2019)

 

Significance

Klebsiella pneumoniae is considered a nosocomial pathogen, usually infecting immunocompromised patients. However, a pathotype of K. pneumoniae, termed hypervirulent K. pneumoniae (hvKp), has emerged and is spreading throughout the community, causing severe, often fatal, disease in healthy individuals. Moreover, reports on multidrug-resistant hvKp isolates are increasing in frequency. It is imperative that strategies to combat hvKp begin immediately to prevent further dissemination of this new class of “superbugs.” Here, we show that bioconjugate vaccines targeting the capsule of hvKp can provide immunity and protection against extremely lethal hvKp strains. Further, we demonstrate that bioconjugation is a promising technology for rapid development of efficacious vaccines against emerging bacterial threats.

 

Abstract

Hypervirulent Klebsiella pneumoniae (hvKp) is globally disseminating as a community-acquired pathogen causing life-threatening infections in healthy individuals. The fact that a dose as little as 50 bacteria is lethal to mice illustrates the dramatic increase of virulence associated with hvKp strains compared with classical K. pneumoniae (cKp) strains, which require lethal doses greater than 107 bacteria. Until recently, these virulent strains were mostly antibiotic-susceptible. However, multidrug-resistant (MDR) hvKp strains have been emerging, spawning a new generation of hypervirulent “superbugs.” The mechanisms of hypervirulence are not fully defined, but overproduction of capsular polysaccharide significantly impedes host clearance, resulting in increased pathogenicity of hvKp strains. While there are more than 80 serotypes of K. pneumoniae, the K1 and K2 serotypes cause the vast majority of hypervirulent infections. Therefore, a glycoconjugate vaccine targeting these 2 serotypes could significantly reduce hvKp infection. Conventionally, glycoconjugate vaccines are manufactured using intricate chemical methodologies to covalently attach purified polysaccharides to carrier proteins, which is widely considered to be technically challenging. Here we report on the recombinant production and analytical characterization of bioconjugate vaccines, enzymatically produced in glycoengineered Escherichia coli cells, against the 2 predominant hypervirulent K. pneumoniae serotypes, K1 and K2. The K. pneumoniae bioconjugates are immunogenic and efficacious, protecting mice against lethal infection from 2 hvKp strains, NTUH K-2044 and ATCC 43816. This preclinical study constitutes a key step toward preventing further global dissemination of hypervirulent MDR hvKp strains.

glycoconjugate – bioconjugation – vaccine – hypervirulent Klebsiella pneumoniae

Keywords: Klebsiella pneumoniae; Vaccines; Animal models.

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#WGS to Identify #Drivers of #Carbapenem-Resistant #Klebsiella pneumoniae #Transmission Within and Between Regional Long-Term Acute Care #Hospitals (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Whole Genome Sequencing to Identify Drivers of Carbapenem-Resistant Klebsiella pneumoniae Transmission Within and Between Regional Long-Term Acute Care Hospitals

Jennifer H. Han [MD, MSCE], Zena Lapp [BA], Frederic Bushman [PhD], Ebbing Lautenbach [MD, MPH, MSCE], Ellie J.C. Goldstein [MD], Lisa Mattei [PhD], Casey E. Hofstaedter [BS],Dorothy Kim [BS], Irving Nachamkin [DrPH, MPH], Charles Garrigan [MB], Tanya Jain [MS], Warren Bilker [PhD], Hannah M. Wolford [MSPH], Rachel B. Slayton [PhD, MPH],Jacqueleen Wise [BS], Pam Tolomeo [MPH], Evan S. Snitkin [PhD]

DOI: 10.1128/AAC.01622-19

 

ABSTRACT

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an antibiotic resistance threat of the highest priority. Given the limited treatment options for this multidrug-resistant organism (MDRO), there is an urgent need for targeted strategies to prevent transmission. Here, we applied whole-genome sequencing to a comprehensive collection of clinical isolates to reconstruct regional transmission pathways, and analyzed this transmission network in the context of statewide patient transfer data and patient-level clinical data to identify drivers of regional transmission. We found that high regional CRKP burden was due to a small number of regional introductions, with subsequent regional proliferation occurring via patient transfers among healthcare facilities. While CRKP was predicted to be imported into each facility multiple times, there was substantial variation in the ratio of intra-facility transmission events per importation, indicating that amplification occurs unevenly across regional facilities. While myriad factors likely influence intra-facility transmission rates, an understudied one is the potential for clinical characteristics of colonized and infected patient to influence their propensity for transmission. Supporting the contribution of high-risk patients to elevated transmission rates, we observed that CRKP colonized and infected patients in high transmission facilities had higher rates of carbapenem use, malnutrition, old age and dialysis. This study highlights the potential for regional infection prevention efforts that are grounded in genomic epidemiology to identify patients and facilities that make the greatest contribution to regional MDRO prevalence, thereby facilitating the design of precision interventions of maximal impact.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Klebsiella pneumoniae; Nosocomial outbreaks.

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#Factors associated with #fatality due to #avian #influenza A(#H7N9) #infection in #China (Clin Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Clin Infect Dis. 2019 Aug 16. pii: ciz779. doi: 10.1093/cid/ciz779. [Epub ahead of print]

Factors associated with fatality due to avian influenza A(H7N9) infection in China.

Zheng S1,2,3, Zou Q2,3, Wang X2,3, Bao J2,3, Yu F2,3, Guo F4, Liu P5, Shen Y6, Wang Y7, Yang S1, Wu W1, Sheng J1, Vijaykrishna D8,9, Gao H1,4, Chen Y1,2,3.

Author information: 1 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, P.R. China. 2 Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, P.R. China. 3 Center of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, P.R. China. 4 Department of Infectious Diseases, Shulan (Hangzhou) Hospital, Hangzhou, P.R. China. 5 Department of Infectious Diseases, The second hospital of Ningbo, Ningbo, P.R. China. 6 Department of Infectious and Immune Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, P.R. China. 7 Department of Pulmonary and Critical Care Medicine, Center for Respiratory Diseases, National Clinical Research Center of Respiratory Diseases, China-Japan Friendship Hospital, Beijing, P.R. China. 8 Department of Microbiology, Biomedicine Discovery Institute, Monash University, Victoria, Australia. 9 World Health Organization Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.

 

Abstract

BACKGROUND:

The high case fatality rate of influenza A H7N9 infected patients has been a major clinical concern.

METHODS:

To identify the common causes of death due to H7N9 as well as identify risk factors associated with the high inpatient mortality, we retrospectively collected clinical treatment information from 350 hospitalized human cases of H7N9 virus in mainland China during 2013-2017, of which 109 (31.1%) had died, and systematically analysed the patient’s clinical characteristics and risk factors for death.

RESULTS:

The median age of infection was 57 years, whereas the median age of mortality was 61 years, significantly older than those survived. In contrast to previous studies, we found nosocomial infections, comprising Acinetobacter baumannii and Klebsiella most commonly associated with secondary bacterial infections, which was likely due to the high utilization of supportive therapies, including mechanical ventilation (52.6%), ECMO (14%), CRRT (19.1%), and artificial liver therapy (9.7%). Age, time from illness onset to antiviral therapy initiation and secondary bacterial infection were independent risk factors for death. Age >65, secondary bacterial infections, and initiation of neuraminidase inhibitors therapy after 5 days from symptom onset were associated with increased risk of death.

CONCLUSIONS:

Fatality among H7N9 virus infected patients occurred rapidly after hospital admission, especially among older patients, and was followed by severe hypoxemia and multisystem organ failure. Our results show that early neuraminidase-inhibitor therapy and reduction of secondary bacterial infections can help reduce mortality.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

KEYWORDS: H7N9; Influenza; Risk factors; zoonotic infection

PMID: 31418813 DOI: 10.1093/cid/ciz779

Keywords: Antivirals; Antibiotics; Avian Influenza; H7N9; Human; China; Klebsiella pneumoniae; Acinetobacter baumannii.

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Towards #endemicity: large-scale #expansion of the #NDM-1-producing #Klebsiella pneumoniae ST11 lineage in #Poland, 2015–16 (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Towards endemicity: large-scale expansion of the NDM-1-producing Klebsiella pneumoniae ST11 lineage in Poland, 2015–16

A Baraniak, M Machulska, D Żabicka, E Literacka, R Izdebski, P Urbanowicz, K Bojarska,M Herda, A Kozińska, W Hryniewicz, M Gniadkowski, NDM-PL Study Group

Journal of Antimicrobial Chemotherapy, dkz315, https://doi.org/10.1093/jac/dkz315

Published: 13 August 2019

 

Abstract

Objectives

In 2015 and 2016 Poland recorded rapid proliferation of New Delhi MBL (NDM)-producing Enterobacterales, with at least 470 and 1780 cases, respectively. We addressed the roles of the Klebsiella pneumoniae ST11 NDM-1 outbreak genotype, already spreading in 2012–14, and of newly imported organisms in this increase.

Methods

The study included 2136 NDM-positive isolates identified between April 2015 and December 2016, following transfer of patients with K. pneumoniae ST147 NDM-1 from Tunisia to Warsaw in March 2015. The isolates were screened by PCR mapping for variants of blaNDM-carrying Tn125-like elements. Selected isolates were typed by PFGE and MLST. NDM-encoding plasmids were analysed by nuclease S1/hybridization, transfer assays, PCR-based replicon typing and PCR mapping.

Results

The organisms were mainly K. pneumoniae containing the Tn125A variant of the ST11 epidemic lineage (n = 2094; ∼98%). Their representatives were of the outbreak pulsotype and ST11, and produced NDM-1, encoded by specific IncFII (pKPX-1/pB-3002cz)-like plasmids. The isolates were recovered in 145 healthcare centres in 13/16 administrative regions, predominantly the Warsaw area. The ‘Tunisian’ genotype K. pneumoniae ST147 NDM-1 Tn125F comprised 18 isolates (0.8%) from eight institutions. The remaining 24 isolates, mostly K. pneumoniae and Escherichia coli of diverse STs, produced NDM-1 or NDM-5 specified by various Tn125 derivatives and plasmids.

Conclusions

The K. pneumoniae ST11 NDM-1 outbreak has dramatically expanded in Poland since 2012, which may bring about a countrywide endemic situation in the near future. In addition, the so-far limited K. pneumoniae ST147 NDM-1 outbreak plus multiple NDM imports from different countries were observed in 2015–16.

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Beta-lactams; NDM1; NDM5; Poland.

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Successful #treatment with #cefiderocol for #compassionate use in a critically ill #patient with #XDR #Acinetobacter baumannii and KPC-producing #Klebsiella pneumoniae: a case report (J Antimicrob Chemother., summary)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Summary, edited.]

Successful treatment with cefiderocol for compassionate use in a critically ill patient with XDR Acinetobacter baumannii and KPC-producing Klebsiella pneumoniae: a case report

Enrico Maria Trecarichi, Angela Quirino, Vincenzo Scaglione, Federico Longhini,Eugenio Garofalo, Andrea Bruni, Eugenio Biamonte, Rosaria Lionello,Francesca Serapide, Maria Mazzitelli, Nadia Marascio, Giovanni Matera,Maria Carla Liberto, Paolo Navalesi, Carlo Torti, IMAGES Group

Journal of Antimicrobial Chemotherapy, dkz318, https://doi.org/10.1093/jac/dkz318

Published: 01 August 2019

___

Sir,

Cefiderocol is a new siderophore cephalosporin, with potent activity against MDR Gram-negative bacilli. It is particularly active against XDR Acinetobacter baumannii(Ab) infections, for which treatment options are quite limited.1–3 Herein, we describe a case of an adult male patient with severe H1N1 influenza complicated by ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) caused by XDR Ab and carbapenemase-producing Klebsiella pneumoniae (KPC-Kp). Nothing remarkable was in his medical history apart from favism and Aarskog–Scott syndrome. In February 2019, due to the onset of acute respiratory failure, he was admitted to a peripheral primary ICU where he was diagnosed with H1N1 influenza…

(…)

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© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Acinetobacter baumannii; Klebsiella pneumoniae; Seasonal Influenza; H1N1pdm09; Pneumonia; Cefiderocol.

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