Predominance of OXA-48 Carbapenemase-Producing Enterobacterales in a Moroccan Hospital

Objective The emergence of carbapenemase-producing Enterobacterales (CPE) is a major concern that is increasingly reported worldwide. Our study aimed at investigating the resistance of CPE isolates in a Moroccan teaching hospital using phenotypic and genotypic methods. Methods Enterobacterales strains from March to June 2018 were collected from different clinical samples. The Enterobacterales isolates resistant to third-generation cephalosporins (3GC) and/or carbapenems were subjected to the Carba NP test and an immunochromatographic test for phenotypic detection. Detection of extended-spectrum β-lactamases (ESBL) was also performed following standards. Molecular screening of carbapenemases genes (OXA-48, NDM, blaKPC, blaIMP, blaVIM, and blaOXA-24, blaOXA-23, OXA-51, OXA-58) using conventional multiplex PCR assays was also performed on 143 isolates. Results Enterobacterales represented 52.7% with a proportion of 21.8% of bacteria resistant to 3GC and/or carbapenems. Within 143 isolates MDR to 3GC, K. pneumoniae, E. coli, and E. cloacae represent 53.1%, 40.6%, and 6.3%, respectively. These strains were isolated mainly from urinary samples (74.8%) in patients admitted to emergency and surgical units. 81.1% of strains are producing ESBL and 29% are carbapenemase producers as confirmed by the Carba NP test, immunochromatographic test, and molecular testing. OXA-48 carriers represent 83.3% of these strains, followed by NDM with 16.7%. blaKPC, blaIMP, blaVIM, and blaOXA-24, blaOXA-23, OXA-51, OXA-58 were not detected in any of these bacteria. Conclusions A high rate of CPE carrying OXA-48 among Enterobacterales resistant to 3GC and/or carbapenems isolates was found. Strict observance of hospital hygiene measures and more rational use of antibiotics are mandatory. Implantation of carbapenemases detection should be encouraged in our hospital settings to estimate the true burden of the CPE.

[1]  Soraa Nabila,et al.  Antibiotic resistance patterns of carbapenemase-producing Enterobacterales in Mohammed VI University Hospital of Marrakech, Morocco. , 2022, Infectious Diseases Now.

[2]  J. Lavigne,et al.  Dissemination of OXA-48- and NDM-1-Producing Enterobacterales Isolates in an Algerian Hospital , 2022, Antibiotics.

[3]  Wenmin Zhao,et al.  Epidemiology and genotypic characteristics of carbapenem resistant Enterobacterales in Henan, China: A multicentre study. , 2022, Journal of global antimicrobial resistance.

[4]  S. Chevalier,et al.  Prevention and control of highly antibiotic-resistant bacteria in a Pacific territory: feedback from New Caledonia between 2004 and 2020. , 2021, Infectious diseases now.

[5]  J. Rolain,et al.  Dissemination of Carbapenemases (OXA-48, NDM and VIM) Producing Enterobacteriaceae Isolated from the Mohamed VI University Hospital in Marrakech, Morocco , 2021, Antibiotics.

[6]  Babita Sharma,et al.  Phenotypic Detection of Carbapenemase Production in Carbapenem-Resistant Enterobacteriaceae by Modified Hodge Test and Modified Strip Carba NP Test , 2021, Journal of Laboratory Physicians.

[7]  J. Rolain,et al.  Phenotypic and genotypic characterization of clinical carbapenem-resistant Enterobacteriaceae isolates from Sokoto, northwest Nigeria , 2020, New microbes and new infections.

[8]  N. Sunil-Chandra,et al.  Epidemiology of multidrug-resistant Enterobacteriaceae in Sri Lanka: First evidence of blaKPC harboring Klebsiella pneumoniae. , 2020, Journal of infection and public health.

[9]  F. Shahcheraghi,et al.  Evaluation of Phenotypic and Genotypic Characteristics of Carbapnemases-producing Enterobacteriaceae and Its Prevalence in a Referral Hospital in Tehran City , 2020, Iranian journal of pathology.

[10]  M. Khurshid,et al.  Carbapenem Resistance: Mechanisms and Drivers of Global Menace , 2020, Pathogenic Bacteria.

[11]  G. Peirano,et al.  The Global Ascendency of OXA-48-Type Carbapenemases , 2019, Clinical Microbiology Reviews.

[12]  K. Lawrence,et al.  National prevalence estimates for resistant Enterobacteriaceae and Acinetobacter species in hospitalized patients in the United States. , 2019, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[13]  M. Samore,et al.  A systematic review of the epidemiology of carbapenem-resistant Enterobacteriaceae in the United States , 2018, Antimicrobial Resistance & Infection Control.

[14]  Hong Yang,et al.  Epidemiology of Carbapenem-Resistant Enterobacteriaceae Infections: Report from the China CRE Network , 2017, Antimicrobial Agents and Chemotherapy.

[15]  D. van Duin,et al.  The global epidemiology of carbapenemase-producing Enterobacteriaceae , 2017, Virulence.

[16]  F. Shahcheraghi,et al.  Molecular study of carbapenemase genes in clinical isolates of Enterobacteriaceae resistant to carbapenems and determining their clonal relationship using pulsed‐field gel electrophoresis , 2017, Journal of medical microbiology.

[17]  K. Kazmierczak,et al.  In Vitro Activity of Imipenem against Carbapenemase-Positive Enterobacteriaceae Isolates Collected by the SMART Global Surveillance Program from 2008 to 2014 , 2017, Journal of Clinical Microbiology.

[18]  A. Awab,et al.  Les entérobactéries sécrétrices de bêta-lactamases a spectre étendu en urologie a l'hôpital ibn sina de rabat , 2016 .

[19]  C. Girmenia,et al.  Epidemiology of Carbapenem Resistant Klebsiella pneumoniae Infections in Mediterranean Countries , 2016, Mediterranean journal of hematology and infectious diseases.

[20]  M. Kolář,et al.  Primer Evaluation for PCR and its Application for Detection of Carbapenemases in Enterobacteriaceae , 2016, Jundishapur journal of microbiology.

[21]  R. Lynfield,et al.  Epidemiology of Carbapenem-Resistant Enterobacteriaceae in 7 US Communities, 2012-2013. , 2015, JAMA.

[22]  Y. Sekhsokh,et al.  Evaluation of antimicrobial susceptibility of Escherichia coli strains isolated in Rabat University Hospital (Morocco) , 2015, BMC Research Notes.

[23]  C. Hou,et al.  Drug-resistant gene of blaOXA-23, blaOXA-24, blaOXA-51 and blaOXA-58 in Acinetobacter baumannii. , 2015, International journal of clinical and experimental medicine.

[24]  M. Ling,et al.  Risk factors for acquisition of carbapenem resistant Enterobacteriaceae in an acute tertiary care hospital in Singapore , 2015, Antimicrobial Resistance and Infection Control.

[25]  Setegn Eshetie,et al.  Multidrug resistant and carbapenemase producing Enterobacteriaceae among patients with urinary tract infection at referral Hospital, Northwest Ethiopia , 2015, Antimicrobial Resistance and Infection Control.

[26]  S. Richter,et al.  Tigecycline therapy for carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteriuria leads to tigecycline resistance. , 2014, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[27]  P. Nordmann,et al.  The difficult-to-control spread of carbapenemase producers among Enterobacteriaceae worldwide. , 2014, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[28]  P. Srivastava,et al.  Prevalence and antibiogram of Extended Spectrum β-Lactamase (ESBL) producing Gram negative bacilli and further molecular characterization of ESBL producing Escherichia coli and Klebsiella spp. , 2013, Journal of clinical and diagnostic research : JCDR.

[29]  R. Bonomo,et al.  Carbapenem-resistant Enterobacteriaceae: a review of treatment and outcomes. , 2013, Diagnostic microbiology and infectious disease.

[30]  M. E. Wartiti,et al.  Prevalence of Carbapenemase-Producing Enterobacteriaceae in a University Hospital in Rabat, Morocco: A 19-Months Prospective Study. , 2012 .

[31]  G. Daikos,et al.  Carbapenemases in Klebsiella pneumoniae and Other Enterobacteriaceae: an Evolving Crisis of Global Dimensions , 2012, Clinical Microbiology Reviews.

[32]  P. Nordmann,et al.  Rapid Detection of Carbapenemase-producing Enterobacteriaceae , 2012, Emerging infectious diseases.

[33]  J. Kasouati,et al.  In Vitro Activities of Ertapenem and Imipenem against Clinical Extended Spectrum Beta-Lactamase-Producing Enterobacteriaceae Collected in Military Teaching Hospital Mohammed V of Rabat , 2012, Interdisciplinary perspectives on infectious diseases.

[34]  G. Araj,et al.  The threat of carbapenem-resistant Enterobacteriaceae in Lebanon: an update on the regional and local epidemiology. , 2012, Journal of infection and public health.

[35]  V. Miriagou,et al.  Rapid evolution and spread of carbapenemases among Enterobacteriaceae in Europe. , 2012, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[36]  P. Nordmann,et al.  Carbapenem resistance in Enterobacteriaceae: here is the storm! , 2012, Trends in molecular medicine.

[37]  R. Widen,et al.  Rapid detection of carbapenemase genes by multiplex real-time PCR. , 2012, The Journal of antimicrobial chemotherapy.

[38]  M. Falagas,et al.  Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. , 2012, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[39]  P. Nordmann,et al.  Emergence of NDM-1-producing Klebsiella pneumoniae in Morocco. , 2011, The Journal of antimicrobial chemotherapy.

[40]  P. Nordmann,et al.  European dissemination of a single OXA-48-producing Klebsiella pneumoniae clone. , 2011, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[41]  Thierry Naas,et al.  Global Spread of Carbapenemase-producing Enterobacteriaceae , 2011, Emerging infectious diseases.

[42]  D. Raoult,et al.  Real-time PCR assay allows detection of the New Delhi metallo-β-lactamase (NDM-1)-encoding gene in France. , 2011, International journal of antimicrobial agents.

[43]  G. Araj,et al.  First detection of oxacillinase-mediated resistance to carbapenems in Klebsiella pneumoniae from Morocco , 2010, Annals of tropical medicine and parasitology.

[44]  P. Nordmann,et al.  Molecular Epidemiology and Mechanisms of Carbapenem Resistance in Pseudomonas aeruginosa , 2009, Antimicrobial Agents and Chemotherapy.

[45]  J. Quinn,et al.  Genetic Structures at the Origin of Acquisition of the β-Lactamase blaKPC Gene , 2008, Antimicrobial Agents and Chemotherapy.

[46]  V. Jarlier,et al.  Extended broad-spectrum beta-lactamases conferring transferable resistance to newer beta-lactam agents in Enterobacteriaceae: hospital prevalence and susceptibility patterns. , 1988, Reviews of infectious diseases.

[47]  A. Laglaoui,et al.  Phenotypic and Molecular Study of Carbapenemase-Producing Enterobacteriaceae in a Regional Hospital in Northern Morocco , 2019 .