Molecular Epidemiology of Carbapenem-Resistant Acinetobacter baumannii Isolates from Northern Africa and the Middle East

At the Bundeswehr Hospitals of Hamburg and Westerstede, patients repatriated from subtropical war and crisis zones of Northern Africa and the Middle East were medically treated, including microbiological assessment. Within a six-year interval, 16 Acinetobacter spp. strains, including 14 Acinetobacter baumannii (Ab) isolates with resistance against carbapenems and origins in Afghanistan (n = 4), Iraq (n = 2), Libya (n = 2), and Syria (n = 8) were collected. While clonal relationships of Libyan and Syrian strains had been assessed by superficial next generation sequencing (NGS) and “DiversiLab” repetitive elements sequence-based (rep-)PCR so far, this study provides core genome-based sequence typing and thus more detailed epidemiological information. In detail, sequencing allowed a definitive species identification and comparison with international outbreak-associated Ab strains by core genome multi locus sequence typing (cgMLST) and the identification of MLST lineages, as well as the identification of known resistance genes. The sequence analysis allowed for the confirmation of outbreak-associated clonal clusters among the Syrian and Afghan Ab isolates, indicating likely transmission events. The identified acquired carbapenem resistance genes comprised blaOXA-23, blaOXA-58, blaNDM-1, and blaGES-11, next to other intrinsic and acquired, partly mobile resistance-associated genes. Eleven out of 14 Ab isolates clustered with the previously described international clonal lineages IC1 (4 Afghan strains), IC2 (6 Syrian strains), and IC7 (1 Syrian strain). Identified Pasteur sequence types of the 14 Ab strains comprised ST2 (Syrian), ST25 (Libyan), ST32 (Iraqi), ST81 (Afghan), ST85 (Libyan), and ST1112 (Syrian), respectively. In conclusion, the study revealed a broad spectrum of resistance genes in Ab isolated from war-injured patients from Northern Africa and the Middle East, thereby broadening the scarcely available data on locally abundant clonal lineages and resistance mechanisms.

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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.

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Molecular Epidemiology of Carbapenem-Resistant Acinetobacter baumannii Isolated from War-Injured Patients from the Eastern Ukraine

Antibiotics ◽

10.3390/antibiotics9090579 ◽

2020 ◽

Vol 9 (9) ◽

pp. 579

Author(s):

Paul G. Higgins ◽

Ralf Matthias Hagen ◽

Andreas Podbielski ◽

Hagen Frickmann ◽

Philipp Warnke

Keyword(s):

Acinetobacter Baumannii ◽

Core Genome ◽

Acquired Resistance ◽

Sequence Type ◽

Carbapenem Resistant ◽

Next Generation Sequencing Ngs ◽

Injured Patients ◽

Sequence Types ◽

Generation Sequencing ◽

Epidemiological Information

Recently, a total of 32 carbapenem- and fluoroquinolone-resistant Acinetobacter baumannii (Ab) isolates was isolated from war-injured patients who were treated at German Bundeswehr Hospitals, and preliminarily typed by “DiversiLab” repetitive elements sequence-based (rep-) PCR. Core genome-based sequence typing was also used to provide more detailed epidemiological information. From the clusters observed by rep-PCR, selected Ab strains were subjected to Next Generation Sequencing (NGS) in order to compare them with international outbreak-associated Ab strains and to identify MLST (multi-locus sequence type) lineages, as well as to identify known resistance genes. Accordingly, NGS indicated higher diversity than rep-PCR, but also confirmed likely transmission events. The identified acquired carbapenem-resistant genes comprised blaOXA-23, blaOXA-72 and blaGES-12, as well as various other intrinsic and acquired resistance-associated genetic elements. All isolates clustered with the previously identified international clonal lineages IC1, IC2, IC6 and IC7, with corresponding Pasteur sequence types ST1, ST2, ST78 and ST25, respectively. In conclusion, the assessment confirmed a broad spectrum of resistance-associated genes in Ab isolated from war-injured patients from the Eastern Ukraine, and provided the first insights into locally abundant clonal lineages.

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Diversity of sequence types and impact of fitness cost among carbapenem-resistant Acinetobacter baumannii isolates from Tripoli, Libya

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00277-21 ◽

2021 ◽

Author(s):

Antoine G. Abou Fayad ◽

Louis-Patrick Haraoui ◽

Ahmad Sleiman ◽

Mohamad Jaafar ◽

Abdulaziz Zorgani ◽

...

Keyword(s):

Molecular Epidemiology ◽

Acinetobacter Baumannii ◽

Doubling Time ◽

Core Genome ◽

Carbapenem Resistance ◽

Relative Fitness ◽

Fitness Advantage ◽

Carbapenem Resistant ◽

Sequence Types ◽

Hospital Transmission

We investigated the molecular epidemiology of 21 carbapenem-resistant A. baumannii from Libya, and assessed their relative fitness. Core-genome MLST revealed five inter-hospital transmission clusters. Three clusters were associated with the international clones (IC) IC1, IC2, and IC7. Carbapenem-resistance was associated with bla OXA-23, bla GES-11 , or bla NDM-1 . Compared to A. baumannii DSM 30008, the doubling time was similar over 10 hours, but after 16 hours, half the isolates grew to higher densities, suggesting a fitness advantage.

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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.

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Molecular Epidemiology of Carbapenem-Resistant Acinetobacter baumannii From Khartoum State, Sudan

Frontiers in Microbiology ◽

10.3389/fmicb.2021.628736 ◽

2021 ◽

Vol 12 ◽

Author(s):

Leena Al-Hassan ◽

Hana Elbadawi ◽

Einas Osman ◽

Sara Ali ◽

Kamal Elhag ◽

...

Keyword(s):

Antibiotic Resistance ◽

Molecular Epidemiology ◽

Acinetobacter Baumannii ◽

Core Genome ◽

Treatment Options ◽

Resistance Mechanisms ◽

Multiple Antibiotic Resistance ◽

Resistance Determinants ◽

Carbapenem Resistant ◽

Allelic Differences

Carbapenem resistant Acinetobacter baumannii (CRAb) is an important global pathogen contributing to increased morbidity and mortality in hospitalized patients, due to limited alternative treatment options. Nine international clonal (IC) lineages have been identified in many countries worldwide, however, data still lacks from some parts of the world, particularly in Africa. We hereby present the molecular epidemiology of MDR A. baumannii from four hospitals in Khartoum, Sudan, collected from 2017 to 2018. Forty-two isolates were whole-genome sequenced, and subsequent molecular epidemiology was determined by core genome MLST (cgMLST), and their resistomes identified. All isolates had an array of diverse antibiotic resistance mechanisms conferring resistance to multiple classes of antibiotics. We found a predominance (88%) of IC2 (with the intrinsic OXA-66 and acquired OXA-23), and some with NDM-1. IC2 isolates were sub-divided into 4 STs separated by 5 to 431 allelic differences, and with evidence of seven transmission clusters. Isolates belonging to IC1, IC5, and IC9 were also identified. These data illustrate that MDR IC2 A. baumannii are widely distributed in Khartoum hospitals and are in possession of multiple antibiotic resistance determinants.

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WGS-Based Analysis of Carbapenem-Resistant Acinetobacter baumannii in Vietnam and Molecular Characterization of Antimicrobial Determinants and MLST in Southeast Asia

Antibiotics ◽

10.3390/antibiotics10050563 ◽

2021 ◽

Vol 10 (5) ◽

pp. 563

Author(s):

Gamal Wareth ◽

Jörg Linde ◽

Ngoc H. Nguyen ◽

Tuan N. M. Nguyen ◽

Lisa D. Sprague ◽

...

Keyword(s):

Southeast Asia ◽

Acinetobacter Baumannii ◽

Core Genome ◽

Action Plan ◽

Carbapenem Resistant ◽

Global Threat ◽

Next Generation Sequencing Ngs ◽

Sequence Types ◽

Generation Sequencing

Carbapenem-resistant Acinetobacter baumannii (A. baumannii, CRAb) is an emerging global threat for healthcare systems, particularly in Southeast Asia. Next-generation sequencing (NGS) technology was employed to map genes associated with antimicrobial resistance (AMR) and to identify multilocus sequence types (MLST). Eleven strains isolated from humans in Vietnam were sequenced, and their AMR genes and MLST were compared to published genomes of strains originating from Southeast Asia, i.e., Thailand (n = 49), Myanmar (n = 38), Malaysia (n = 11), Singapore (n = 4) and Taiwan (n = 1). Ten out of eleven Vietnamese strains were CRAb and were susceptible only to colistin. All strains harbored ant(3”)-IIa, armA, aph(6)-Id and aph(3”) genes conferring resistance to aminoglycosides, and blaOXA-51 variants and blaADC-25 conferring resistance to ß-lactams. More than half of the strains harbored genes that confer resistance to tetracyclines, sulfonamides and macrolides. The strains showed high diversity, where six were assigned to sequence type (ST)/2, and two were allocated to two new STs (ST/1411-1412). MLST analyses of 108 strains from Southeast Asia identified 19 sequence types (ST), and ST/2 was the most prevalent found in 62 strains. A broad range of AMR genes was identified mediating resistance to ß-lactams, including cephalosporins and carbapenems (e.g., blaOXA-51-like, blaOXA-23, blaADC-25, blaADC-73, blaTEM-1, blaNDM-1), aminoglycosides (e.g., ant(3”)-IIa, aph(3”)-Ib, aph(6)-Id, armA and aph(3’)-Ia), phenicoles (e.g., catB8), tetracyclines (e.g., tet.B and tet.39), sulfonamides (e.g., sul.1 and sul.2), macrolides and lincosamide (e.g., mph.E, msr.E and abaF). MLST and core genome MLST (cgMLST) showed an extreme diversity among the strains. Several strains isolated from different countries clustered together by cgMLST; however, different clusters shared the same ST. Developing an action plan on AMR, increasing awareness and prohibiting the selling of antibiotics without prescription must be mandatory for this region. Such efforts are critical for enforcing targeted policies on the rational use of carbapenem compounds and controlling AMR dissemination and emergence in general.

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Variants of Tn 6924 , a Novel Tn 7 Family Transposon Carrying the bla NDM Metallo-β-Lactamase and 14 Copies of the aphA6 Amikacin Resistance Genes Found in Acinetobacter baumannii

Microbiology Spectrum ◽

10.1128/spectrum.01745-21 ◽

2022 ◽

Author(s):

Riti Mann ◽

Rayane Rafei ◽

Cindy Gunawan ◽

Christopher J. Harmer ◽

Mohammad Hamidian

Keyword(s):

Acinetobacter Baumannii ◽

Resistance Genes ◽

Resistance Mechanisms ◽

Sequence Type ◽

Content Type ◽

Carbapenem Resistant ◽

Globally Distributed

To date, efforts to study the resistance mechanisms of carbapenem-resistant Acinetobacter baumannii have been largely focused on the two major globally distributed clones (GC1 and GC2). ST85 is an emerging sequence type, and unlike other clones, it is associated with the carriage of the bla NDM gene.

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Molecular Epidemiology and Clone Transmission of Carbapenem-Resistant Acinetobacter baumannii in ICU Rooms

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.633817 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiufeng Zhang ◽

Fangping Li ◽

Furqan Awan ◽

Hongye Jiang ◽

Zhenling Zeng ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Insertion Sequence ◽

Core Genome ◽

Carbapenem Resistance ◽

Multidrug Resistant ◽

Chi Square ◽

The Core ◽

Carbapenem Resistant ◽

Significant Difference ◽

Chi Square Test

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a major cause of nosocomial infections and hospital outbreaks worldwide, remaining a critical clinical concern. Here we characterized and investigated the phylogenetic relationships of 105 CRAB isolates from an intensive care unit from one hospital in China collected over six years. All strains carried blaOXA-23, blaOXA-66 genes for carbapenem resistance, also had high resistance gene, virulence factor, and insertion sequence burdens. Whole-genome sequencing revealed all strains belonged to ST2, the global clone CC2. The phylogenetic analysis based on the core genome showed all isolates were dominated by a single lineage of three clusters and eight different clones. Two clones were popular during the collection time. Using chi-square test to identify the epidemiologically meaningful groupings, we found the significant difference in community structure only existed in strains from separation time. The haplotype and median-joining network analysis revealed genetic differences appeared among clusters and changes occurred overtime in the dominating cluster. Our results highlighted substantial multidrug-resistant CRAB burden in the hospital ICU environment demonstrating potential clone outbreak in the hospital.

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In vitro activity of sulbactam/durlobactam against global isolates of carbapenem-resistant Acinetobacter baumannii

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa208 ◽

2020 ◽

Vol 75 (9) ◽

pp. 2616-2621 ◽

Cited By ~ 2

Author(s):

Harald Seifert ◽

Carina Müller ◽

Danuta Stefanik ◽

Paul G Higgins ◽

Alita Miller ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Carbapenem Resistance ◽

Resistance Mechanisms ◽

The Novel ◽

In Vitro Activity ◽

Carbapenem Resistant ◽

Excellent Activity ◽

Acinetobacter Spp ◽

Lactamase Inhibitor

Abstract Objectives To evaluate the activity of the novel broad-spectrum serine β-lactamase inhibitor durlobactam (ETX2514) combined with sulbactam against global isolates of carbapenem-resistant Acinetobacter baumannii with defined carbapenem resistance mechanisms compared with reference antimicrobials with known activity against Acinetobacter spp. Methods The susceptibility of 246 carbapenem-resistant non-duplicate A. baumannii isolates to sulbactam/durlobactam, amikacin, colistin, imipenem/sulbactam/durlobactam, imipenem, meropenem, minocycline and sulbactam was tested using broth microdilution. Isolates were obtained from various body sites from patients in 37 countries and from six world regions between 2012 and 2016. Identification of carbapenem resistance mechanisms and assignment to A. baumannii clonal lineages was based on WGS. Results Sulbactam/durlobactam showed excellent activity comparable to colistin but superior to amikacin, minocycline and sulbactam. The sulbactam/durlobactam MIC50/90 values were 1/4 and 2/4 mg/L and the colistin MIC50/90 values were 0.5 and 1 mg/L, respectively. Comparatively, amikacin, minocycline and sulbactam MIC50/90 values were 256/≥512, 2/16 and 16/64 mg/L, respectively. Conclusions Sulbactam/durlobactam had excellent in vitro potency against A. baumannii isolates, including those that were resistant to imipenem/meropenem, amikacin, minocycline and colistin, compared with other compounds. Sulbactam/durlobactam has the potential to become a useful addition to the limited armamentarium of drugs that can be used to treat this problem pathogen.

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Prevalence of OXA-Type β-Lactamase Genes among Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates in Thailand

Antibiotics ◽

10.3390/antibiotics9120864 ◽

2020 ◽

Vol 9 (12) ◽

pp. 864

Author(s):

Krit Thirapanmethee ◽

Thayapa Srisiri-a-nun ◽

Jantana Houngsaitong ◽

Preecha Montakantikul ◽

Piyatip Khuntayaporn ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Tertiary Care ◽

Carbapenem Resistance ◽

Resistance Mechanisms ◽

Clinical Isolates ◽

Health Concern ◽

Drug Of Choice ◽

Carbapenem Resistant ◽

Resistance Rates ◽

Tertiary Care Hospitals

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a critical health concern for the treatment of infectious diseases. The aim of this study was to investigate the molecular epidemiology of CRAB emphasizing the presence of oxacillinase (OXA)-type β-lactamase-encoding genes, one of the most important carbapenem resistance mechanisms. In this study, a total of 183 non-repetitive CRAB isolates collected from 11 tertiary care hospitals across Thailand were investigated. As a result, the blaoxa-51-like gene, an intrinsic enzyme marker, was detected in all clinical isolates. The blaoxa-23-like gene was presented in the majority of isolates (68.31%). In contrast, the prevalence rates of blaoxa-40/24-like and blaoxa-58-like gene occurrences in CRAB isolates were only 4.92% and 1.09%, respectively. All isolates were resistant to carbapenems, with 100% resistance to imipenem, followed by meropenem (98.91%) and doripenem (94.54%). Most isolates showed high resistance rates to ciprofloxacin (97.81%), ceftazidime (96.72%), gentamicin (91.26%), and amikacin (80.87%). Interestingly, colistin was found to be a potential drug of choice due to the high susceptibility of the tested isolates to this antimicrobial (87.98%). Most CRAB isolates in Thailand were of ST2 lineage, but some belonged to ST25, ST98, ST129, ST164, ST215, ST338, and ST745. Further studies to monitor the spread of carbapenem-resistant OXA-type β-lactamase genes from A. baumannii in hospital settings are warranted.

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