Spread of imipenem-resistant Acinetobacter baumannii co-expressing OXA-23 and GES-11 carbapenemases in Lebanon

Halat, Dalal Hammoudi; Moubareck, Carole Ayoub; Hakime, Noha; Houmani, M.; Barakat, Angelique; Najjar, Zeina; Suleiman, Mohammed; Fayad, Nancy; Sarraf, R.; Sarkis, Dolla Karam

doi:10.1016/j.ijid.2015.05.015

Cited by 43 publications

(39 citation statements)

References 32 publications

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“…An extremely high rate of carbapenem resistance (90%) was detected among the A. baumannii isolates. This rate, however, is very similar to that reported from a nation-wide study (Hammoudi et al, 2015a) where the prevalence of CRAB isolates was 88%. These findings suggest an immediate need for the implementation of effective infection control measures and antibiotic stewardship programs in Lebanese hospitals.…”

Section: Discussionsupporting

confidence: 90%

“…Moreover, CRAB isolates were found to increase in prevalence in this country throughout the past decade (Hamouche and Sarkis, 2012). In 2012, 88% of 724 A. baumannii isolates recovered from various Lebanese hospitals were found to be resistant to imipenem (Hammoudi et al, 2015a). Although OXA-24-like (Hammoudi et al, 2015b) and OXA-58-like (Zarrilli et al, 2008) have been detected in this country, OXA-23-like seems to be the most prevalent among CRAB isolates (Rafei et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Acinetobacter baumannii Isolated from Lebanese Patients: Phenotypes and Genotypes of Resistance, Clonality, and Determinants of Pathogenicity

Hajjar

Suárez

Daoud

2016

Front. Cell. Infect. Microbiol.

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Introduction: Acinetobacter baumannii is a nosocomial pathogen that usually affects critically ill patients. High mortality rates have been associated with MDR A. baumannii infections. Carbapenem resistance among these isolates is increasing worldwide and is associated with certain International Clones (ICs) and oxacillinases (OXAs). Moreover, this organism possesses a wide range of virulence factors, whose expression is not yet fully understood. In this study, clinical A. baumannii isolates are characterized in terms of antibiotic resistance, mechanisms of carbapenem resistance, clonality, and virulence.Materials and Methods: A. baumannii clinical isolates (n = 90) where obtained from a tertiary care center in Beirut, Lebanon. API 20NE strips in addition to the amplification of blaOXA−51−like were used for identification. Antibiotic susceptibility testing by disk diffusion was then performed in addition to PCRs for the detection of the most commonly disseminated carbapenemases. Clonality was determined by tri-locus PCR typing and doubling times were determined for isolates with varying susceptibility profiles. Biofilm formation, hemolysis, siderophore production, proteolytic activity, and surface motility was then determined for all the isolates. Statistical analysis was then performed for the determination of associations.Results and Discussion: 81 (90%) of the isolates were resistant to carbapenems. These high rates are similar to other multi-center studies in the country suggesting the need of intervention on a national level. 74 (91.3%) of the carbapenem resistant isolates harbored blaOXA−23−like including two that also harbored blaOXA−24−like. 88.9% of the A. baumannii isolates pertained to ICII and three other international clones were detected, showing the wide dissemination of clones into geographically distinct locations. Virulence profiles were highly diverse and no specific pattern was observed. Nevertheless, an association between motility, siderophore production, and biofilm formation was detected (p < 0.05).Conclusions: A very high rate of carbapenem resistance was detected, showing the need for immediate intervention. IC II and OXA-23-like were the most disseminated, reflecting their international dissemination. No specific associations were made between virulence and resistance, but instead associations among certain virulence factors were found. Investigating a more clonally diverse pool of isolates could help in the determination of associations between virulence and resistance.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Acinetobacter baumannii Isolated from Lebanese Patients: Phenotypes and Genotypes of Resistance, Clonality, and Determinants of Pathogenicity

Hajjar

Suárez

Daoud

2016

Front. Cell. Infect. Microbiol.

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“…ISAba1, which belongs to the IS4 family of insertion sequence elements, provides a promoter motif mediating the increased expression of bla OXA-23 and is involved in facilitating its own mobilization not only to A. baumannii but also to Proteus mirabilis (10). Upon its first description in 1995 in A. baumannii, bla OXA-23 carried on plasmids or transposons became widespread and was detected in isolates recovered from the United Kingdom, France, Romania, Brazil, South Korea, United Arab Emirates, Egypt, and Iraq (10,30,31). bla OXA-23 was detected previously in GC2 CRAB isolates in Lebanon and was recognized as being the most common carbapenemase in the country (17,30).…”

Section: Discussionmentioning

confidence: 99%

Whole-Genome-Sequence-Based Characterization of Extensively Drug-Resistant Acinetobacter baumannii Hospital Outbreak

Makke

Bitar

Salloum

et al. 2020

mSphere

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Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important opportunistic pathogen linked to a variety of nosocomial infections and hospital outbreaks worldwide. This study aimed at investigating and characterizing a CRAB outbreak at a large tertiary hospital in Lebanon. A total of 41 isolates were collected and analyzed using pulsed-field gel electrophoresis (PFGE). Whole-genome sequencing (WGS) was performed on all the isolates, and long-read PacBio sequencing was used to generate reference genomes. The multilocus sequence types (MLST), repertoire of resistance genes, and virulence factors were determined from the sequencing data. The plasmid content was analyzed both in silico and using the A. baumannii PCR-based replicon typing (AB-PBRT) method. Genome analysis initially revealed two clones, one carrying blaOXA-23 on Tn2006 (ST-1305, ST-195, and ST-218) and another carrying blaOXA-72 on pMAL-1 (ST-502 and ST-2059, a new ST), with the latter having two subclones, as revealed using the Bayesian transmission network. All isolates were extensively drug resistant (XDR). WGS analysis revealed the transmission pathways and demonstrated the diversity of CRAB isolates and mobile genetic elements in this health care setting. Outbreak detection using WGS and immediate implementation of infection control measures contribute to restraining the spread and decreasing mortality. IMPORTANCE Carbapenem-resistant Acinetobacter baumannii (CRAB) has been implicated in hospital outbreaks worldwide. Here, we present a whole-genome-based investigation of an extensively drug-resistant CRAB outbreak rapidly spreading and causing high incidences of mortality at numerous wards of a large tertiary hospital in Lebanon. This is the first study of its kind in the region. Two circulating clones were identified using a combination of molecular typing approaches, short- and long-read sequencing and Bayesian transmission network analysis. One clone carried blaOXA-23 on Tn2006 (ST-1305, ST-195, and ST-218), and another carried blaOXA-72 on a pMAL-1 plasmid (ST-502 and ST-2059, a new ST). A pMAL-2 plasmid was circulating between the two clones. The approaches implemented in this study and the obtained findings facilitate the tracking of outbreak scenarios in Lebanon and the region at large.

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“…bla IMP , bla VIM , bla NDM , bla OXA−23−like , bla OXA −24− like , bla OXA−48 , bla OXA −51− like , bla OXA−58−like , bla GES , bla KPC , were tested for by Simplex PCR using the primers listed in Table 1 (Moubareck et al, 2009; Dallenne et al, 2010; Ardebili et al, 2014; Rafei et al, 2014). Positive and negative controls for the tested genes were provided from previous studies performed in the lab (Moubareck et al, 2009; Hammoudi et al, 2015). …”

Section: Methodsmentioning

confidence: 99%

In vitro Evaluation of the Colistin-Carbapenem Combination in Clinical Isolates of A. baumannii Using the Checkerboard, Etest, and Time-Kill Curve Techniques

Soudeiha

Dahdouh

Azar

et al. 2017

Front. Cell. Infect. Microbiol.

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The worldwide increase in the emergence of carbapenem resistant Acinetobacter baumannii (CRAB) calls for the investigation into alternative approaches for treatment. This study aims to evaluate colistin-carbapenem combinations against Acinetobacter spp., in order to potentially reduce the need for high concentrations of antibiotics in therapy. This study was conducted on 100 non-duplicate Acinetobacter isolates that were collected from different patients admitted at Saint George Hospital-University Medical Center in Beirut. The isolates were identified using API 20NE strips, which contain the necessary agents to cover a panel of biochemical tests, and confirmed by PCR amplification of blaOXA−51−like. Activities of colistin, meropenem and imipenem against Acinetobacter isolates were determined by ETEST and microdilution methods, and interpreted according to the guidelines of the Clinical and Laboratory Standards Institute. In addition, PCR amplifications of the most common beta lactamases contributing to carbapenem resistance were performed. Tri locus PCR–typing was also performed to determine the international clonality of the isolates. Checkerboard, ETEST and time kill curves were then performed to determine the effect of the colistin-carbapenem combinations. The synergistic potential of the combination was then determined by calculating the Fractional Inhibitory Concentration Index (FICI), which is an index that indicates additivity, synergism, or antagonism between the antimicrobial agents. In this study, 84% of the isolates were resistant to meropenem, 78% to imipenem, and only one strain was resistant to colistin. 79% of the isolates harbored blaOXA−23−like and pertained to the International Clone II. An additive effect for the colistin-carbapenem combination was observed using all three methods. The combination of colistin-meropenem showed better effects as compared to colistin-imipenem (p < 0.05). The colistin-meropenem and colistin-imipenem combinations also showed a decrease of 2.6 and 2.8-fold, respectively in the MIC of colistin (p < 0.001). Time kill assays additionally showed synergistic effects for a few isolates, and no bacterial re-growth was detected following a 24 h incubation. Our study showed that the combination of colistin with carbapenems could be a promising antimicrobial strategy in treating CRAB infections and potentially lowering colistin toxicity related to higher doses used in colistin monotherapy.

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Spread of imipenem-resistant Acinetobacter baumannii co-expressing OXA-23 and GES-11 carbapenemases in Lebanon

Abstract: This survey established baseline evidence of OXA-23 and GES-11-producing A. baumannii in Lebanon, indicating the need for further surveillance.

Cited by 43 publications

References 32 publications

Acinetobacter baumannii Isolated from Lebanese Patients: Phenotypes and Genotypes of Resistance, Clonality, and Determinants of Pathogenicity

Acinetobacter baumannii Isolated from Lebanese Patients: Phenotypes and Genotypes of Resistance, Clonality, and Determinants of Pathogenicity

Whole-Genome-Sequence-Based Characterization of Extensively Drug-Resistant Acinetobacter baumannii Hospital Outbreak

In vitro Evaluation of the Colistin-Carbapenem Combination in Clinical Isolates of A. baumannii Using the Checkerboard, Etest, and Time-Kill Curve Techniques

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