Emergence of Carbapenem-Resistant Non-baumannii Species of Acinetobacter Harboring ablaOXA-51-Like Gene That Is Intrinsic to A. baumannii

ABSTRACTTheblaOXA-51-like gene, originally intrinsic toAcinetobacter baumannii, had been detected in two clones ofAcinetobacter nosocomialisand one clone ofAcinetobactergenomic species “Close to 13TU.” TheseblaOXA-51-like genes, all preceded by ISAba1, were located on plasmids that might have originated withA. baumannii. The plasmid-borne ISAba1--blaOXA-51-like confers a high level of carbapenem resistance and affects the accuracy of usingblaOXA-51-like detection as a tool for differentiatingA. baumanniifrom otherAcinetobacterspecies.

Download Full-text

Types and Prevalence of Carbapenem-Resistant Acinetobacter calcoaceticus-Acinetobacter baumannii Complex in Northern Taiwan

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00779-13 ◽

2013 ◽

Vol 58 (1) ◽

pp. 201-204 ◽

Cited By ~ 12

Author(s):

Wen-Shyang Hsieh ◽

Nai-Yu Wang ◽

Jou-An Feng ◽

Li-Chuan Weng ◽

Hsueh-Hsia Wu

Keyword(s):

Acinetobacter Baumannii ◽

Medical Center ◽

Carbapenem Resistance ◽

Acinetobacter Calcoaceticus ◽

Pulsed Field Gel Electrophoresis ◽

Content Type ◽

Carbapenem Resistant ◽

Acinetobacter Baumannii Complex ◽

High Level ◽

Northern Taiwan

ABSTRACTThe frequency of the carbapenem-resistantAcinetobacter calcoaceticus-Acinetobacter baumannii(CRACB) complex increases annually in our hospitals. However, the types and prevalence of carbapenemases among isolates still remain unclear. In this study, we identified and collected 672 carbapenem-resistant isolates from a medical center in Northern Taiwan between April and December of 2010. There were 577 genospecies 2 (Acinetobacter baumannii), 79 genospecies 13TU, and 16 genospecies 3 isolates. The isolates had an acquiredblaOXA-24-like gene, which was confirmed by sequencing for the encoded OXA-72 carbapenemase, and were often associated with high-level carbapenem resistance. These CRACB complex isolates remained susceptible to colistin (100%). The genotyping of isolates was conducted using pulsed-field gel electrophoresis with ApaI digestion. In most clonally related groups, patients were from both branch hospitals. The results indicate that interhospital dissemination of clones occurred. This study provides updated data on the types and prevalence of the CRACB complex. In addition, it presents a warning on the emergence and spread of CRACB complex harboringblaOXA-24-like genes in northern Taiwan.

Download Full-text

Emergence and Distribution of Plasmids Bearing the blaOXA-51-Like Gene with an Upstream ISAba1 in Carbapenem-Resistant Acinetobacter baumannii Isolates in Taiwan

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00764-10 ◽

2010 ◽

Vol 54 (11) ◽

pp. 4575-4581 ◽

Cited By ~ 79

Author(s):

Te-Li Chen ◽

Yi-Tzu Lee ◽

Shu-Chen Kuo ◽

Po-Ren Hsueh ◽

Feng-Yee Chang ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Copy Number ◽

Recombinant Plasmid ◽

Gene Dosage ◽

Carbapenem Resistance ◽

Carbapenem Resistant ◽

Genomic Species ◽

High Level

ABSTRACT The bla OXA-51-like gene with an upstream ISAba1 (ISAba1-bla OXA-51-like gene) was originally found on the chromosomes of carbapenem-resistant or -susceptible Acinetobacter baumannii isolates. However, a plasmid-borne ISAba1-bla OXA-51-like gene has recently been identified in Acinetobacter genomic species 13TU and several A. baumannii isolates in Taiwan, and all of the isolates are carbapenem resistant. This study aimed to characterize the plasmids bearing the ISAba1-bla OXA-51-like gene and their significance in A. baumannii. Among the 117 ISAba1-bla OXA-51-like-harboring isolates collected from 10 hospitals in Taiwan, 58 isolates (49.6%) from 24 clones had the genes located on plasmids that likely originated from a common progenitor. Among the 58 isolates, four had additional copy of the ISAba1-bla OXA-51-like gene on their chromosomes. Based on the analysis of these four isolates, the plasmid-located ISAba1-bla OXA-51-like gene appeared to be acquired via one-ended transposition (Tn6080). The isolates with a plasmid bearing the ISAba1-bla OXA-51-like gene had higher rates of resistance to imipenem (98% versus 46.6%; P < 0.001) and meropenem (98% versus 69%; P = 0.019) than those with the genes chromosomally encoded, which is most likely due to increased gene dosage provided by the higher copy number of associated plasmids. Transformation with a recombinant plasmid harboring only the ISAba1-bla OXA-51-like gene was enough to confer a high level of carbapenem resistance to A. baumannii, eliminating the possible contribution of other factors on the original plasmids. This study demonstrated that the carbapenem resistance-associated plasmids carrying the ISAba1-bla OXA-51-like gene are widespread in A. baumannii strains in Taiwan.

Download Full-text

High-Level Carbapenem Resistance in OXA-232-Producing Raoultella ornithinolytica Triggered by Ertapenem Therapy

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01335-19 ◽

2019 ◽

Vol 64 (1) ◽

Cited By ~ 2

Author(s):

Alina Iovleva ◽

Roberta T. Mettus ◽

Christi L. McElheny ◽

Marissa P. Griffith ◽

Mustapha M. Mustapha ◽

...

Keyword(s):

Rapid Development ◽

Carbapenem Resistance ◽

Resistant Isolate ◽

Clinical Microbiology Laboratory ◽

Loss Of Function ◽

Content Type ◽

Carbapenem Resistant ◽

Class D ◽

Fold Reduction ◽

High Level

ABSTRACT OXA-232 is an OXA-48-group class D β-lactamase that hydrolyzes expanded-spectrum cephalosporins and carbapenems at low levels. Clinical strains producing OXA-232 are sometimes susceptible to carbapenems, making it difficult to identify them in the clinical microbiology laboratory. We describe the development of carbapenem resistance in sequential clinical isolates of Raoultella ornithinolytica carrying blaOXA-232 in a hospitalized patient, where the ertapenem MIC increased from 0.5 μg/ml to 512 μg/ml and the meropenem MIC increased from 0.125 μg/ml to 32 μg/ml during the course of ertapenem therapy. Whole-genome sequencing (WGS) analysis identified loss-of-function mutations in ompC and ompF in carbapenem-resistant isolates that were not present in the initial carbapenem-susceptible isolate. Complementation of a carbapenem-resistant isolate with an intact ompF gene resulted in 16- to 32-fold reductions in carbapenem MICs, whereas complementation with intact ompC resulted in a 2-fold reduction in carbapenem MICs. Additionally, blaOXA-232 expression increased 2.9-fold in a carbapenem-resistant isolate. Rapid development of high-level carbapenem resistance in initially carbapenem-susceptible OXA-232-producing R. ornithinolytica under selective pressure from carbapenem therapy highlights the diagnostic challenges in detecting Enterobacteriaceae strains producing this inefficient carbapenemase.

Download Full-text

Multicity Outbreak of Carbapenem-Resistant Acinetobacter baumannii Isolates Producing the Carbapenemase OXA-40

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00116-06 ◽

2006 ◽

Vol 50 (9) ◽

pp. 2941-2945 ◽

Cited By ~ 127

Author(s):

Karen Lolans ◽

Thomas W. Rice ◽

L. Silvia Munoz-Price ◽

John P. Quinn

Keyword(s):

Acinetobacter Baumannii ◽

Carbapenem Resistance ◽

The United States ◽

Nucleotide Sequencing ◽

Sequencing Analysis ◽

Carbapenem Resistant ◽

Extended Care ◽

Care Facilities ◽

High Level ◽

First Time

ABSTRACT During 2005 we detected a multicity outbreak of infections or colonization due to high-level imipenem-resistant Acinetobacter baumannii (MIC, 64 μg/ml). One hundred isolates from diverse sources were obtained from seven acute-care hospitals and two extended-care facilities; 97% of the isolates belonged to one clone. Susceptibility testing of the first 42 isolates (January to April 2005) revealed broad resistance profiles. Half of the isolates were susceptible to ceftazidime, with many isolates susceptible only to colistin. The level of AmpC β-lactamase expression was stronger in isolates resistant to ceftazidime. PCR and subsequent nucleotide sequencing analysis identified bla OXA-40. The presence of an OXA-40 β-lactamase in these isolates correlated with the carbapenem resistance. By Southern blot analysis, a bla OXA-40-specific probe revealed that the gene was both plasmid and chromosomally located. This is the first time in the United States that such carbapenem resistance in A. baumannii has been attributable to a carbapenemase.

Download Full-text

Accumulation of Antibiotic Resistance Genes in Carbapenem-Resistant Acinetobacter baumannii Isolates Belonging to Lineage 2, Global Clone 1, from Outbreaks in 2012–2013 at a Tehran Burns Hospital

mSphere ◽

10.1128/msphere.00164-20 ◽

2020 ◽

Vol 5 (2) ◽

Cited By ~ 2

Author(s):

Masoumeh Douraghi ◽

Johanna J. Kenyon ◽

Parisa Aris ◽

Mahla Asadian ◽

Sedighe Ghourchian ◽

...

Keyword(s):

Middle East ◽

Acinetobacter Baumannii ◽

Resistance Genes ◽

Carbapenem Resistance ◽

Antibiotic Resistant ◽

Content Type ◽

Carbapenem Resistant ◽

East Region ◽

Lineage 2 ◽

Middle East Region

ABSTRACT The worldwide distribution of carbapenem-resistant Acinetobacter baumannii (CRAB) has become a global concern, particularly in countries where antibiotic prescription is not tightly regulated. However, knowledge of the genomic aspects of CRAB from many parts of the world is still limited. Here, 50 carbapenem-resistant A. baumannii isolates recovered at a single hospital in Tehran, Iran, during several outbreaks in 2012 and 2013 were found to be resistant to multiple antibiotics. They were examined using PCR mapping and multilocus sequence typing (MLST). All Iranian strains belonged to sequence type 328 in the Institut Pasteur MLST scheme (ST328IP), a single-locus variant of ST81IP, and all Iranian strains contained two carbapenem resistance genes, oxa23 and oxa24. The oxa23 gene is in the transposon Tn2006 in AbaR4, which interrupts the chromosomal comM gene. Phylogenetic analysis using whole-genome sequence (WGS) data for 9 isolates showed that they belonged to the same clade, designated the ST81/ST328 clade, within lineage 2 of global clone 1 (GC1). However, there were two groups that included either KL13 or KL18 at the K locus (KL) for capsular polysaccharide synthesis and either a tet39 or an aadB resistance gene, respectively. The genetic context of the resistance genes was determined, and the oxa24 (OXA-72 variant) and tet39 (tetracycline resistance) genes were each in a pdif module in different plasmids. The aadB gene cassette (which encodes gentamicin, kanamycin, and tobramycin resistance) was harbored by pRAY*, and the aphA6 gene (which encodes amikacin resistance) and sul2 gene (which encodes sulfamethoxazole resistance) were each harbored by a different plasmid. The sequences obtained here will underpin future studies of GC1 CRAB strains from the Middle East region. IMPORTANCE Carbapenem-resistant Acinetobacter baumannii strains are among the most critical antibiotic-resistant bacteria causing hospital-acquired infections and treatment failures. The global spread of two clones has been responsible for the bulk of the resistance, in particular, carbapenem resistance. However, there is a substantial gap in our knowledge of which clones and which specific lineages within each clone are circulating in many parts of the world, including Africa and the Middle East region. This is the first genomic analysis of carbapenem-resistant A. baumannii strains from Iran. All the isolates, from a single hospital, belonged to lineage 2 of global clone 1 (GC1) but fell into two groups distinguished by genes in the locus for capsule biosynthesis. The analysis suggests a potential origin of multiply antibiotic-resistant lineage 2 in the Middle East region and highlights the ongoing evolution of carbapenem-resistant GC1 A. baumannii strains. It will enhance future studies on the local and global GC1 population structure.

Download Full-text

Co-infection of ST2IP carbapenem-resistant Acinetobacter baumannii with SARS-CoV-2 in the patients admitted to a Tehran tertiary referral hospital

BMC Infectious Diseases ◽

10.1186/s12879-021-06642-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Alireza Abdollahi ◽

Amir Aliramezani ◽

Mohammadreza Salehi ◽

Mahsa Norouzi Shadehi ◽

Sedighe Ghourchian ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Genetic Relatedness ◽

Carbapenem Resistance ◽

Underlying Disease ◽

Referral Hospital ◽

Clinical Samples ◽

Tertiary Referral ◽

Tertiary Referral Hospital ◽

Carbapenem Resistant ◽

High Level

Abstract Background Carbapenem-resistant Acinetobacter baumannii (CRAB) is among the most concerning cause of healthcare-associated infections (HAI) due to its high level of antibiotic resistance and high mortality. In the era of the COVID-19 pandemic, the key priority of infection control committees is to contain the dissemination of antibiotic resistant Gram-negative bacteria. Here, we aimed to timely recognize the emergence of CRAB in COVID-19 cases admitted to the wards of a tertiary referral hospital and to identify the genetic relatedness of the isolates. Methods From 30 March to 30 May 2020, a total of 242 clinical samples from COVID-19 cases were screened for CRAB isolates using standard microbiologic and antibiotic susceptibility tests. The PCRs targeting oxa23, oxa24, oxa58, blaTEM and blaNDM-1 genes were performed. Two multiplex PCRs for identifying the global clones (GC) of A. baumannii were also performed. The sequence type of CRABs was determined using Institut Pasteur (IP) multilocus sequence typing (MLST) scheme. Results Eighteen CRAB isolates were recovered from COVID-19 patients with the mean age of 63.94 ± 13.8 years. All but 4 COVID-19 patients co-infected with CRAB were suffering from an underlying disease. Death was recorded as the outcome in ICUs for 9 (50%) COVID-19 patients co-infected with CRAB. The CRAB isolates belong to GC2 and ST2IP and carried the oxa23 carbapenem resistance gene. Conclusion This study demonstrated the co-infection of CRAB isolates and SARS-CoV-2 in the patients admitted to different ICUs at a referral hospital in Tehran. The CRAB isolates were found to belong to ST2IP, share the oxa23 gene and to have caused several outbreaks in the wards admitting COVID-19 patients.

Download Full-text

Therapeutic Efficacy of LN-1-255 in Combination with Imipenem in Severe Infection Caused by Carbapenem-Resistant Acinetobacter baumannii

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01092-19 ◽

2019 ◽

Vol 63 (10) ◽

Cited By ~ 3

Author(s):

Juan Carlos Vázquez-Ucha ◽

Marta Martínez-Guitián ◽

María Maneiro ◽

Kelly Conde-Pérez ◽

Laura Álvarez-Fraga ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Combined Therapy ◽

Severe Infection ◽

Carbapenem Resistance ◽

Antibacterial Treatment ◽

Bacterial Burden ◽

Content Type ◽

Carbapenem Resistant ◽

Class D

ABSTRACT The carbapenem-hydrolyzing class D β-lactamases (CHDLs) are the main mechanism of carbapenem resistance in Acinetobacter baumannii. CHDLs are not effectively inactivated by clinically available β-lactam-type inhibitors. We have previously described the in vitro efficacy of the inhibitor LN-1-255 in combination with carbapenems. The aim of this study was to compare the efficacy of LN-1-255 with that of imipenem in murine pneumonia using A. baumannii strains carrying their most extended carbapenemases, OXA-23 and OXA-24/40. The blaOXA-23 and blaOXA-24/40 genes were cloned into the carbapenem-susceptible A. baumannii ATCC 17978 strain. Clinical isolates Ab1 and JC12/04, producing the enzymes OXA-23 and OXA-24/40, respectively, were used in the study. Pharmacokinetic (PK) parameters were determined. An experimental pneumonia model was used to evaluate the efficacy of the combined imipenem–LN-1-255 therapy. MICs of imipenem decreased between 32- and 128-fold in the presence of LN-1-255. Intramuscular treatment with imipenem–LN-1-255 (30/50 mg/kg) decreased the bacterial burden by (i) 4 and 1.7 log10 CFU/g lung in the infection with the ATCC 17978-OXA-23 and Ab1 strains, respectively, and by (ii) 2.5 and 4.5 log10 CFU/g lung in the infection produced by the ATCC 17978-OXA-24/40 and the JC12/04 strains, respectively. In all assays, combined therapy offered higher protection against pneumonia than that provided by monotherapy. No toxicity was observed in treated mice. Imipenem treatment combined with LN-1-255 treatment significantly reduced the severity of infection by carbapenem-resistant A. baumannii strains carrying CHDLs. Preclinical assays demonstrated the potential of LN-1-255 and imipenem therapy as a new antibacterial treatment.

Download Full-text

Carbapenem-Resistant Non-Glucose-Fermenting Gram-Negative Bacilli: the Missing Piece to the Puzzle

Journal of Clinical Microbiology ◽

10.1128/jcm.03264-15 ◽

2016 ◽

Vol 54 (7) ◽

pp. 1700-1710 ◽

Cited By ~ 47

Author(s):

Thomas J. Gniadek ◽

Karen C. Carroll ◽

Patricia J. Simner

Keyword(s):

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Gene Transfer ◽

Infection Control ◽

Acinetobacter Baumannii ◽

Carbapenem Resistance ◽

Gram Negative ◽

Content Type ◽

Carbapenem Resistant ◽

Ferment Glucose

The non-glucose-fermenting Gram-negative bacilliPseudomonas aeruginosaandAcinetobacter baumanniiare increasingly acquiring carbapenem resistance. Given their intrinsic antibiotic resistance, this can cause extremely difficult-to-treat infections. Additionally, resistance gene transfer can occur between Gram-negative species, regardless of their ability to ferment glucose. Thus, the acquisition of carbapenemase genes by these organisms increases the risk of carbapenemase spread in general. Ultimately, infection control practitioners and clinical microbiologists need to work together to determine the risk carried by carbapenem-resistant non-glucose-fermenting Gram-negative bacilli (CR-NF) in their institution and what methods should be considered for surveillance and detection of CR-NF.

Download Full-text

Evaluation of Clonality and Carbapenem Resistance Mechanisms among Acinetobacter baumannii-Acinetobacter calcoaceticus Complex and Enterobacteriaceae Isolates Collected in European and Mediterranean Countries and Detection of Two Novel β-Lactamases, GES-22 and VIM-35

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03930-14 ◽

2014 ◽

Vol 58 (12) ◽

pp. 7358-7366 ◽

Cited By ~ 35

Author(s):

Mariana Castanheira ◽

Sarah E. Costello ◽

Leah N. Woosley ◽

Lalitagauri M. Deshpande ◽

Todd A. Davies ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Carbapenem Resistance ◽

Acinetobacter Calcoaceticus ◽

Resistance Mechanisms ◽

The Novel ◽

Intrinsic Resistance ◽

Content Type ◽

Carbapenem Resistant ◽

Mediterranean Countries ◽

Class 1

ABSTRACTWe evaluated doripenem-resistantAcinetobacter baumannii-Acinetobacter calcoaceticuscomplex (ACB;n= 411) andEnterobacteriaceae(n= 92) isolates collected from patients from 14 European and Mediterranean countries during 2009 to 2011 for the presence of carbapenemase-encoding genes and clonality. Following susceptibility testing, carbapenem-resistant (doripenem MIC, >2 μg/ml) isolates were screened for carbapenemases. New β-lactamase genes were expressed in a common background and susceptibility was tested. Class 1 integrons were sequenced. Clonality was evaluated by pulsed-field gel electrophoresis and multilocus sequence typing (Pasteur scheme). Relative expression of β-lactam intrinsic resistance mechanisms was determined for carbapenemase-negativeEnterobacteriaceae. ACB andEnterobacteriaceaedisplayed 58.9 and 0.9% doripenem resistance, respectively.blaOXA-23,blaOXA-58, andblaOXA-24/OXA-40were detected among 277, 77, and 29 ACB, respectively (in 8, 6, and 5 countries). Ten Turkish isolates carriedblaGES-11orblaGES-22. GES-22 (G243A and M169L mutations in GES-1) had an extended-spectrum β-lactamase profile. A total of 33 clusters of ≥2 ACB isolates were observed, and 227 isolates belonged to sequence type 2/international clone II. Other international clones were limited to Turkey and Israel. Doripenem-resistantEnterobacteriaceaeincreased significantly (0.7 to 1.6%), and 15blaKPC-2- and 22blaKPC-3-carrying isolates, mostly belonging to clonal complexes 11 and 258, were observed.Enterobacteriaceaeisolates producing OXA-48 (n= 16; in Turkey and Italy), VIM-1 (n= 10; in Greece, Poland, and Spain), VIM-26 (n= 1; in Greece), and IMP-19, VIM-4, and the novel VIM-35 (n= 1 each from Poland) were detected. VIM-35 had one substitution compared to VIM-1 (A235T) and a similar susceptibility profile. One or more resistance mechanisms were identified in 4/6 carbapenemase-negativeEnterobacteriaceae. This broad evaluation confirms results from country-specific surveys and shows a highly diverse population of carbapenemase-producing ACB andEnterobacteriaceaein Europe and Mediterranean countries.

Download Full-text

Insights into the complete genomes of carbapenem-resistant Acinetobacter baumannii harbouring bla OXA-23, bla OXA-420 and bla NDM-1 genes using a hybrid-assembly approach

Access Microbiology ◽

10.1099/acmi.0.000140 ◽

2020 ◽

Vol 2 (8) ◽

Author(s):

Saranya Vijayakumar ◽

Chand Wattal ◽

Oberoi J.K. ◽

Sanjay Bhattacharya ◽

Karthick Vasudevan ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Type Species ◽

Carbapenem Resistance ◽

Complete Characterization ◽

Hybrid Assembly ◽

Content Type ◽

Link Type ◽

Type Iv ◽

Carbapenem Resistant ◽

Complete Genomes

Carbapenem resistance in Acinetobacter baumannii is due to bla OXA-23, which is endemic in India. Recently, the sporadic presence of bla OXA-58 as well as the occurrence of dual carbapenemases were observed. The mobility as well as the dissemination of these resistance genes were mainly mediated by various mobile genetic elements. The present study was aimed at characterizing the genetic arrangement of bla OXA-23, bla NDM-1 and bla OXA-58 identified in two complete genomes of carbapenem-resistant A. baumannii (CRAB). Complete genomes obtained using a hybrid-assembly approach revealed the accurate arrangement of Tn2006 with bla OXA-23, ISAba125 with bla NDM and ISAba3 with bla OXA-58. In addition, the association of IntI1 integrase with the bla CARB-2 gene and several virulence factors required for type-IV pili assembly, motility and biofilm formation have been identified. The current study provided deeper insight into the complete characterization of insertion sequences and transposons associated with the carbapenem-resistant genes using short reads of IonTorrent PGM and long reads of MinIon in A. baumannii .

Download Full-text