carbapenem – ETIDIoH

Increase in #HA #Carbapenem-Resistant #Acinetobacter baumannii #Infection and #Colonization in an Acute Care #Hospital During a Surge in #COVID19 Admissions — #NJ, February–July 2020 (MMWR Morb Mortal Wkly Rep., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), MMWR Morbidity and Mortality Weekly Report, full page: (LINK). Abstract, edited.]

Increase in Hospital-Acquired Carbapenem-Resistant Acinetobacter baumannii Infection and Colonization in an Acute Care Hospital During a Surge in COVID-19 Admissions — New Jersey, February–July 2020

Early Release / December 1, 2020 / 69

Stephen Perez, PhD1,2; Gabriel K. Innes, VMD, PhD2; Maroya Spalding Walters, PhD3; Jason Mehr, MPH2; Jessica Arias2; Rebecca Greeley, MPH2; Debra Chew, MD4

Summary

What is already known about this topic?
- Carbapenem-resistant Acinetobacter baumannii (CRAB) causes health care–associated infections that are challenging to contain and often linked to infection prevention and control (IPC) breaches.
What is added by this report?
- A New Jersey hospital reported a cluster of 34 CRAB cases that peaked during a surge in COVID-19 hospitalizations. Strategies to preserve continuity of care led to deviations in IPC practices; CRAB cases decreased when normal operations resumed.
What are the implications for public health practice?
- Hospitals managing surges of patients with COVID-19 might be vulnerable to outbreaks of multidrug-resistant organism (MDRO) infections. Maintaining IPC best practices (e.g., MDRO surveillance and hand hygiene and environmental cleaning audits) to the extent possible could mitigate spread.

Abstract

Carbapenem-resistant Acinetobacter baumannii (CRAB), an opportunistic pathogen primarily associated with hospital-acquired infections, is an urgent public health threat (1). In health care facilities, CRAB readily contaminates the patient care environment and health care providers’ hands, survives for extended periods on dry surfaces, and can be spread by asymptomatically colonized persons; these factors make CRAB outbreaks in acute care hospitals difficult to control (2,3). On May 28, 2020, a New Jersey hospital (hospital A) reported a cluster of CRAB infections during a surge in patients hospitalized with coronavirus disease 2019 (COVID-19). Hospital A and the New Jersey Department of Health (NJDOH) conducted an investigation, and identified 34 patients with hospital-acquired multidrug-resistant CRAB infection or colonization during February–July 2020, including 21 (62%) who were admitted to two intensive care units (ICUs) dedicated to caring for COVID-19 patients. In late March, increasing COVID-19–related hospitalizations led to shortages in personnel, personal protective equipment (PPE), and medical equipment, resulting in changes to conventional infection prevention and control (IPC) practices. In late May, hospital A resumed normal operations, including standard IPC measures, as COVID-19 hospitalizations decreased, lessening the impact of personnel and supply chain shortages on hospital functions. CRAB cases subsequently returned to a pre–COVID-19 baseline of none to two cases monthly. The occurrence of this cluster underscores the potential for multidrug-resistant organisms (MDROs) to spread during events when standard hospital practices might be disrupted; conventional IPC strategies should be reinstated as soon as capacity and resources allow.

(…)

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Keywords: Antibiotics; Drugs Resistance; Carbapenem; Acinetobacter baumannii; SARS-CoV-2; COVID-19; Nosocomial Outbreaks; USA.

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#NDM-β-Lactamase-5–Producing #Escherichia coli in Companion #Animals, #USA (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 26, Number 2—February 2020 / Research Letter

New Delhi Metallo-β-Lactamase-5–Producing Escherichia coli in Companion Animals, United States

Stephen D. Cole, Laura Peak, Gregory H. Tyson, Renate Reimschuessel, Olgica Ceric, and Shelley C. Rankin

Author affiliations: University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA (S.D. Cole, S.C. Rankin); Louisiana State University, Baton Rouge, Louisiana USA (L. Peak); US Food and Drug Administration, Silver Spring, Maryland, USA (G.H. Tyson, R. Reimscheussel, O. Ceric)

Abstract

We report isolation of a New Delhi metallo-β-lactamase-5–producing carbapenem-resistant Escherichia coli sequence type 167 from companion animals in the United States. Reports of carbapenem-resistant Enterobacteriaceae in companion animals are rare. We describe a unique cluster of blaNDM-5–producing E. coli in a veterinary hospital.

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Keywords: Antibiotics; Drugs Resistance; Carbapenem; Beta-lactams; NDM1; USA.

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Novel Subclone of #Carbapenem-Resistant #Klebsiella pneumoniae Sequence Type 11 with Enhanced #Virulence and Transmissibility, #China (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 26, Number 2—February 2020 / Research

Novel Subclone of Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 11 with Enhanced Virulence and Transmissibility, China

Kai Zhou1, Tingting Xiao1, Sophia David1, Qin Wang, Yanzi Zhou, Lihua Guo, David Aanensen, Kathryn E. Holt, Nicholas R. Thomson, Hajo Grundmann2, Ping Shen2, and Yonghong Xiao2

Author affiliations: First Affiliated Hospital of Southern University of Science and Technology (Shenzhen People’s Hospital); Shenzhen, China (K. Zhou); The Second Clinical Medical College of Jinan University, Shenzhen (K. Zhou); Zhejiang University, Hangzhou, China (T. Xiao, Q. Wang, Y. Zhou, L. Guo, P. Shen, Y. Xiao); Centre for Genomic Pathogen Surveillance, Cambridge, UK (S. David, D. Aanensen); University of Melbourne, Melbourne, Victoria, Australia (K.-E. Holt); London School of Hygiene and Tropical Medicine, London, UK (K.E. Holt, N.R. Thomson); Wellcome Trust Sanger Centre, Cambridge (N.R. Thomson); University of Freiburg, Freiburg, Germany (H. Grundmann).

Abstract

We aimed to clarify the epidemiologic and clinical importance of evolutionary events that occurred in carbapenem-resistant Klebsiella pneumoniae (CRKP). We collected 203 CRKP causing bloodstream infections in a tertiary hospital in China during 2013–2017. We detected a subclonal shift in the dominant clone sequence type (ST) 11 CRKP in which the previously prevalent capsular loci (KL) 47 had been replaced by KL64 since 2016. Patients infected with ST11-KL64 CRKP had a significantly higher 30-day mortality rate than other CRKP-infected patients. Enhanced virulence was further evidenced by phenotypic tests. Phylogenetic reconstruction demonstrated that ST11-KL64 is derived from an ST11-KL47–like ancestor through recombination. We identified a pLVPK-like virulence plasmid carrying rmpA and peg-344 in ST11-KL64 exclusively from 2016 onward. The pLVPK-like–positive ST11-KL64 isolates exhibited enhanced environmental survival. Retrospective screening of a national collection identified ST11-KL64 in multiple regions. Targeted surveillance of this high-risk CRKP clone is urgently needed.

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

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Restoring #colistin sensitivity in colistin-resistant #Ecoli: Combinatorial use of MarR inhibitor with efflux pump inhibitor (Sci Rep., abstract)

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

Sci Rep. 2019 Dec 25;9(1):19845. doi: 10.1038/s41598-019-56325-x.

Restoring colistin sensitivity in colistin-resistant E. coli: Combinatorial use of MarR inhibitor with efflux pump inhibitor.

Sundaramoorthy NS1, Suresh P2, Selva Ganesan S2, GaneshPrasad A1, Nagarajan S3.

Author information: 1 Center for Research on Infectious Diseases, School of Chemical and Biotechnology, SASTRA Deemed to be University, Thanjavur, Tamil Nadu, India. 2 Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed to be University, Thanjavur, Tamil Nadu, India. 3 Center for Research on Infectious Diseases, School of Chemical and Biotechnology, SASTRA Deemed to be University, Thanjavur, Tamil Nadu, India. sai@scbt.sastra.edu.

Abstract

Antibiotics like colistin are the last resort to deal with infections by carbapenem-resistant Enterobacteriaceae (CREB). Resistance to colistin severely restricts therapeutic options. To tackle this dire situation, urgent measures to restore colistin sensitivity are needed. In this study, whole-genome sequencing of colistin-resistant E. coli strain was performed and the genome analysis revealed that the strain belonged to the sequence type ST405. Multiple mutations were observed in genes implicated in colistin resistance, especially those related to the L-Ara-4-N pathway but mgrB was unmutated and mcr1-9 genes were missing. MarR inhibitor salicylate was used to re-sensitize this strain to colistin, which increased the negative charge on the cell surface especially in colistin resistant E. coli (U3790 strain) and thereby facilitated a decrease in colistin MIC by 8 fold. It is indeed well known that MarR inhibition by salicylate triggers the expression of AcrAB efflux pumps through MarA. So, in order to fully restore colistin sensitivity, a potent efflux pump inhibitor (BC1), identified earlier by this group was employed. The combination of colistin with both salicylate and BC1 caused a remarkable 6 log reduction in cell counts of U3790 in time-kill assay. Infection of muscle tissue of zebrafish with U3790 followed by various treatments showed that the combination of colistin + salicylate + BC1 was highly effective in reducing bioburden in infected muscle tissue by 4 log fold. Thus, our study shows that a combination of MarR inhibitor to enhance colistin binding and efflux pump inhibitor to reduce colistin extrusion was highly effective in restoring colistin sensitivity in colistin-resistant clinical isolate of E. coli in vitro and in vivo.

PMID: 31882661 DOI: 10.1038/s41598-019-56325-x

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Keywords: Antibiotics; Drugs Resistance; Carbapenem; Colistin; Enterobacteriaceae.

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#Vaccine #Protection against #MDR #Klebsiella pneumoniae in a Nonhuman Primate Model of Severe #LRTI (MBio, abstract)

[Source: MBio, full page: (LINK). Abstract, edited.]

Vaccine Protection against Multidrug-Resistant Klebsiella pneumoniae in a Nonhuman Primate Model of Severe Lower Respiratory Tract Infection

Natalia Malachowa, Scott D. Kobayashi, Adeline R. Porter, Brett Freedman, Patrick W. Hanley, Jamie Lovaglio, Greg A. Saturday, Donald J. Gardner, Dana P. Scott, Amanda Griffin, Kathleen Cordova, Dan Long, Rebecca Rosenke, Daniel E. Sturdevant, Daniel Bruno, Craig Martens, Barry N. Kreiswirth, Frank R. DeLeo

Paul Keim, Editor

DOI: 10.1128/mBio.02994-19

ABSTRACT

Klebsiella pneumoniae is a human gut communal organism and notorious opportunistic pathogen. The relative high burden of asymptomatic colonization by K. pneumoniae is often compounded by multidrug resistance—a potential problem for individuals with significant comorbidities or other risk factors for infection. A carbapenem-resistant K. pneumoniae strain classified as multilocus sequence type 258 (ST258) is widespread in the United States and is usually multidrug resistant. Thus, treatment of ST258 infections is often difficult. Inasmuch as new preventive and/or therapeutic measures are needed for treatment of such infections, we developed an ST258 pneumonia model in cynomolgus macaques and tested the ability of an ST258 capsule polysaccharide type 2 (CPS2) vaccine to moderate disease severity. Compared with sham-vaccinated animals, those vaccinated with ST258 CPS2 had significantly less disease as assessed by radiography 24 h after intrabronchial installation of 108 CFU of ST258. All macaques vaccinated with CPS2 ultimately developed ST258-specific antibodies that significantly enhanced serum bactericidal activity and killing of ST258 by macaque neutrophils ex vivo. Consistent with a protective immune response to CPS2, transcripts encoding inflammatory mediators were increased in infected lung tissues obtained from CPS-vaccinated animals compared with control, sham-vaccinated macaques. Taken together, our data provide support for the idea that vaccination with ST258 CPS can be used to prevent or moderate infections caused by ST258. As with studies performed decades earlier, we propose that this prime-boost vaccination approach can be extended to include multiple capsule types.

IMPORTANCE

Multidrug-resistant bacteria continue to be a major problem worldwide, especially among individuals with significant comorbidities and other risk factors for infection. K. pneumoniae is among the leading causes of health care-associated infections, and the organism is often resistant to multiple classes of antibiotics. A carbapenem-resistant K. pneumoniae strain known as multilocus sequence type 258 (ST258) is the predominant carbapenem-resistant Enterobacteriaceae in the health care setting in the United States. Infections caused by ST258 are often difficult to treat and new prophylactic measures and therapeutic approaches are needed. To that end, we developed a lower respiratory tract infection model in cynomolgus macaques in which to test the ability of ST258 CPS to protect against severe ST258 infection.

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Keywords: Antibiotics; Drugs Resistance; Carbapenem; Klebsiella pneumoniae; Vaccines; Animal models.

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#Carbapenem-Resistant Gram-Negative #Infections in #Children (Antimicrob Agents Chemother., abstract)

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

Carbapenem-Resistant Gram-Negative Infections in Children.

David Aguilera-Alonso, Luis Escosa-García, Jesús Saavedra-Lozano, Emilia Cercenado, Fernando Baquero-Artigao

DOI: 10.1128/AAC.02183-19

ABSTRACT

Carbapenem-resistant organisms (CRO) are a major global public health threat. Enterobacterales through carbapenemase production hydrolyze almost all β-lactams. Infections caused by CRO are challenging to treat due to the limited number of antimicrobial options. This leads to significant morbidity and mortality. Over the last few years, several new antibiotics effective against CRO have been approved. Some of them (e.g., plazomicin or imipenem-cilastatin-relebactam) are currently only approved for adults; others (e.g., ceftazidime-avibactam) have recently been approved for children. Recommendations for antibiotic therapy of CRO infections in pediatric patients are based on evidence mainly from adult studies. The availability of pediatric pharmacokinetics and safety data is the cornerstone to broaden the use of proposed agents in adults to the pediatric population. This article provides a comprehensive review of the current knowledge regarding infections caused by CRO with a focus on children which includes epidemiology, risk factors, outcomes and antimicrobial therapy management, with particular attention to new antibiotics.

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Keywords: Antibiotics; Drugs Resistance; Carbapenem; Gram-negative bacteria; Pediatrics.

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#XDR #Klebsiella pneumoniae ST307 #outbreak, north-eastern #Germany, June to October 2019 (Euro Surveill., abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

Extensively drug-resistant Klebsiella pneumoniae ST307 outbreak, north-eastern Germany, June to October 2019

Sebastian Haller1, Rolf Kramer1, Karsten Becker5, Jürgen A Bohnert5, Tim Eckmanns1, Jörg B Hans6, Jane Hecht1, Claus-Dieter Heidecke5, Nils-Olaf Hübner5, Axel Kramer5, Kathleen Klaper2, Martina Littmann4, Lennart Marlinghaus6, Bernd Neumann2, Yvonne Pfeifer2, Niels Pfennigwerth6, Simone Rogge4, Katharina Schaufler7, Andrea Thürmer3, Guido Werner2, Sören Gatermann6

Affiliations: 1 Robert Koch Institute, Department for Infectious Disease Epidemiology, Berlin, Germany; 2 Robert Koch Institute, Division of Nosocomial Pathogens and Antibiotic Resistance, Wernigerode, Germany; 3 Robert Koch Institute, Genome Sequencing Unit, Berlin, Germany; 4 Regional Public Health Authority Mecklenburg-Western Pomerania, Rostock, Germany; 5 University Medicine Greifswald, Greifswald, Germany; 6 National Reference Centre for multidrug-resistant Gram-negative bacteria, Ruhr University Bochum, Bochum, Germany; 7 Institute of Pharmacy, University of Greifswald, Greifswald, Germany

Correspondence: Sebastian Haller

Citation style for this article: Haller Sebastian, Kramer Rolf, Becker Karsten, Bohnert Jürgen A, Eckmanns Tim, Hans Jörg B, Hecht Jane, Heidecke Claus-Dieter, Hübner Nils-Olaf, Kramer Axel, Klaper Kathleen, Littmann Martina, Marlinghaus Lennart, Neumann Bernd, Pfeifer Yvonne, Pfennigwerth Niels, Rogge Simone, Schaufler Katharina, Thürmer Andrea, Werner Guido, Gatermann Sören. Extensively drug-resistant Klebsiella pneumoniae ST307 outbreak, north-eastern Germany, June to October 2019. Euro Surveill. 2019;24(50):pii=1900734. https://doi.org/10.2807/1560-7917.ES.2019.24.50.1900734

Received: 03 Dec 2019; Accepted: 12 Dec 2019

Abstract

From June to October 2019, 17 patients (six infected, 11 colonised) with an extensively drug-resistant (XDR) Klebsiella pneumoniae strain were notified from four Western Pomerania medical facilities. The XDR K. pneumoniae produced carbapenemases NDM-1 and OXA-48, and was only susceptible to chloramphenicol, tigecycline and cefiderocol. Synergistic activity was observed for the combination of aztreonam plus ceftazidime-avibactam. Genomic analyses showed all isolates belonged to K. pneumoniae sequence type 307. Control measures and further investigations are ongoing.

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

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A #cluster of #colistin- and #carbapenem-resistant #Klebsiella pneumoniae carrying #blaNDM-1 and #mcr-8.2 (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

A cluster of colistin- and carbapenem-resistant Klebsiella pneumoniae carrying blaNDM-1 and mcr-8.2

Ke Ma, Yu Feng, Lu Liu, Zhihong Yao, Zhiyong Zong

The Journal of Infectious Diseases, jiz519, https://doi.org/10.1093/infdis/jiz519

Published: 11 December 2019

Abstract

Background

Klebsiella pneumoniae resistant to both carbapenems and colistin imposes severe challenges for management. Here we report a cluster of five carbapenem-resistant K. pneumoniae clinical strains belonging to ST1 and K57 types, four of which were also resistant to colistin, from two hospitals.

Methods

The five strains were subjected to whole genome sequencing (WGS) using the short-read Illumina HiSeq platform and two strains were also selected for long-read WGS using MinION. Clonal relatedness of the five strains was determined based on single nucleotide polymorphisms (SNPs). Conjugation experiments were performed to obtain self-transmissible plasmids.

Results

All five strains carried the carbapenemase-encoding gene blaNDM-1, whereas the four colistin-resistant strains also harbored a new variant of the mcr-8 colistin resistance gene, namely mcr-8.2. Mcr-8.2 differs from Mcr-8.1 by four amino acid substitutions (A51V, A232S, N365Y, and N480K). mcr-8.2 was located on a large, hybrid, non-self-transmissible plasmid containing IncQ, IncR, and IncFII replicons, whereas blaNDM-1 was carried by self-transmissible IncX3 plasmids. Phylogenetic analysis based on SNPs revealed that the five strains were likely to have a common origin.

Conclusion

Both the intra- and inter-hospital transfer of strains carrying mcr-8 and blaNDM-1 were identified, which represents an emerging threat for clinical management and infection control.

colistin resistance, mcr, plasmid, Klebsiella pneumoniae

Topic: plasmids – colistin – klebsiella pneumoniae – single nucleotide polymorphism – beta-lactamase ndm-1 – carbapenem resistance – whole genome sequencing

This content is only available as a PDF.

Author notes: These authors contributed equally.

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)

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Keywords: Antibiotics; Drugs Resistance; Colistin; Carbapenem; Klebsiella pneumoniae; Nosocomial outbreaks; NDM1.

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#Ceftazidime – #avibactam to treat life-threatening #infections from #carbapenem #resistant #pathogens in critically ill mechanically ventilated patients (Antimicrob Agents Chemother., abstract)

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

Ceftazidime-avibactam to treat life-threatening infections from carbapenem resistant pathogens in critically ill mechanically ventilated patients

Vasiliki Tsolaki, Konstantinos Mantzarlis, Athanasios Mpakalis, Ergina Malli, Fotios Tsimpoukas, Athanasia Tsirogianni, Konstantinos Papagiannitsis, Paris Zygoulis, Maria-Eirini Papadonta, Efthimia Petinaki, Demosthenes Makris, Epaminondas Zakynthinos

DOI: 10.1128/AAC.02320-19

ABSTRACT

Data on the effectiveness of ceftazidime-avibactam (CAZ-AVI) in critically ill, mechanically ventilated patients are limited. The present retrospective observational cohort study, which was conducted in two general Intensive Care Units (ICUs) in central Greece, compared critically-ill, mechanically ventilated patients suffering from carbapenem-resistant enterobacteriaceae (CRE) infections receiving CAZ-AVI to patients who received appropriate available antibiotic therapy. Clinical, microbiological outcomes and safety issues were evaluated. A secondary analysis in patients with blood stream infections (BSI) was conducted. Forty-one patients that received CAZ-AVI (CAZ-AVI group) were compared to thirty-six patients receiving antibiotics other than CAZ-AVI (control group). There was significant improvement in the SOFA score on Day 4 and 10 in the CAZ-AVI compared to the control group (p=0.006, and p=0.003 respectively). Microbiological eradication was accomplished in 33/35 (94.3%) in CAZ-AVI group vs 21/31 (67.7%) patients in control group (p=0.021) and clinical cure was observed in 33/41 (80.5%) vs 19/36 (52.8%) patients (p=0.010), respectively. The results were similar in BSI subgroups for both outcomes (p=0.038 and p=0.014, respectively). 28-day survival was 85.4% in the CAZ-AVI and 61.1% in the control group (log Rank=0.035), while there were 2 and 12 relapses in each group (p=0.042). A CAZ-AVI containing regime was independent predictor of survival and clinical cure (OR 5.575, p=0.012 and OR 5.125, p=0.004, respectively) along with illness severity. In conclusion, no significant side effects were reported. A CAZ-AVI containing regime is more effective than other available antibiotic agents for the treatment of CRE infections in the high-risk, mechanically-ventilated, ICU population.

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Keywords: Antibiotics; Drugs Resistance; Carbapenem; Enterobacteriaceae; Ceftazidime; Avibactam; Intensive care.

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LMB-1 producing #Citrobacter freundii from #Argentina, a novel player in the field of MBLs (Int J Antimicrob Agents, abstract)

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

Int J Antimicrob Agents. 2019 Nov 27. pii: S0924-8579(19)30328-0. doi: 10.1016/j.ijantimicag.2019.11.014. [Epub ahead of print]

LMB-1 producing Citrobacter freundii from Argentina, a novel player in the field of MBLs.

Dabos L1, Rodriguez CH2, Nastro M2, Dortet L3, Bonnin R4, Famiglietti A2, Iorga BI5, Vay C2, Naas T6.

Author information: 1 EA7361 “Structure, dynamic, function and expression of broad spectrum β-lactamases”, Paris-Sud University, Faculty of Medicine, Le Kremlin-Bicêtre, France; Joint research Unit EERA « Evolution and Ecology of Resistance to Antibiotics », Institut Pasteur-APHP-University Paris Sud, Paris, France. 2 Departamento de Bioquímica Clinica, Hospital de Clínicas José de San Martín, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina. 3 EA7361 “Structure, dynamic, function and expression of broad spectrum β-lactamases”, Paris-Sud University, Faculty of Medicine, Le Kremlin-Bicêtre, France; Joint research Unit EERA « Evolution and Ecology of Resistance to Antibiotics », Institut Pasteur-APHP-University Paris Sud, Paris, France; Department of Bacteriology-Hygiene, Bicêtre Hospital, APHP, Le Kremlin-Bicêtre, France; French National Reference Center for Antibiotic Resistance, Le Kremlin-Bicêtre, France. 4 EA7361 “Structure, dynamic, function and expression of broad spectrum β-lactamases”, Paris-Sud University, Faculty of Medicine, Le Kremlin-Bicêtre, France; Joint research Unit EERA « Evolution and Ecology of Resistance to Antibiotics », Institut Pasteur-APHP-University Paris Sud, Paris, France; French National Reference Center for Antibiotic Resistance, Le Kremlin-Bicêtre, France. 5 CNRS, UMR3525, Paris, France. 6 EA7361 “Structure, dynamic, function and expression of broad spectrum β-lactamases”, Paris-Sud University, Faculty of Medicine, Le Kremlin-Bicêtre, France; Joint research Unit EERA « Evolution and Ecology of Resistance to Antibiotics », Institut Pasteur-APHP-University Paris Sud, Paris, France; Department of Bacteriology-Hygiene, Bicêtre Hospital, APHP, Le Kremlin-Bicêtre, France; French National Reference Center for Antibiotic Resistance, Le Kremlin-Bicêtre, France. Electronic address: thierry.naas@aphp.fr.

Abstract

Carbapenemase-producing Enterobacterales expressing OXA-48, KPC, NDM, VIM or IMP enzymes are increasingly reported worldwide. We have characterized LMB-1, a novel metallo-β-latamase (MBL) of Ambler class B3 from Citrobacter freundii 164 (Cf164) clinical isolate from Buenos Aires, Argentina. Cf164 displayed reduced susceptibility to carbapenems but gave inconsistent results with carbapenemase confirmatory tests, suggesting the presence of a weak carbapenemase. Analysis of WGS of Cf164 using Resfinder revealed four β-lactamase genes coding for CTX-M-8, PER-2, TEM-1 and CMY-150, a novel chromosomally-encoded CMY variant. Kinetic parameters of purified CMY-150 did not reveal any carbapenemase activity. However, CMY-150 conferred to E. coli higher MIC values for ceftazidime and aztreonam as compared to CMY-2. The in-house developed β-lactamase search software (ResMINER) in WGS data, revealed a novel subclass B3 MBL named LMB-1. LMB-1 conferred to E. coli, resistance to penicillins, to expanded-spectrum cephalosporins and reduced susceptibility to carbapenems. The blaLMB-1 gene was located on a 176-kb IncA/C2 plasmid. LMB-1 shared 99% of amino acid sequence identity with the MBL encoded in the chromosome of Rheinheimera pacifica, it’s likely progenitor. Despite repeated attempts, LMB-1 could not be purified, thus only specific activities could evidence hydrolysis of carbapenems. Here we report CMY-150, a novel CMY-2 variant that confers increased ceftazidime and aztreonam MICs to E. coli and the first description of LMB-1 in Argentina. This work underlines the need for several CPE confirmatory tests, as this novel enzyme might have been missed using only one.

KEYWORDS: CPE; Carbapenemase; Class B3 MBL; Metallo-beta-lactamase

PMID: 31785341 DOI: 10.1016/j.ijantimicag.2019.11.014

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Keywords: Antibiotics; Drugs Resistance; E. Coli; Citrobacter freundii; Carbapenem; Beta-lactams; Argentina.

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