Diversity of carbapenem resistance mechanisms in Acinetobacter baumannii from a Taiwan hospital: spread of plasmid-borne OXA-72 carbapenemase

Acinetobacter baumannii is an important cause of nosocomial infections worldwide. The elucidation of the carbapenem resistance mechanisms of hospital strains is necessary for the effective treatment and prevention of resistance gene transmission. The main mechanism of carbapenem resistance in A. baumannii is carbapenemases, whose expressions are affected by the presence of insertion sequences (ISs) upstream of blaCHDL genes. In this study, 61 imipenem-nonsusceptible A. baumannii isolates were characterized using phenotypic (drug-susceptibility profile using CarbaAcineto NP) and molecular methods. Pulsed field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) methods were utilized for the genotyping. The majority of isolates (59/61) carried one of the following acquired blaCHDL genes: blaOXA-24-like (39/59), ISAba1-blaOXA-23-like (14/59) or ISAba3-blaOXA-58-like (6/59). Whole genome sequence analysis of 15 selected isolates identified the following intrinsic blaOXA-66 (OXA-51-like; n = 15) and acquired class D β-lactamases (CHDLs): ISAba1-blaOXA-23 (OXA-23-like; n = 7), ISAba3-blaOXA-58-ISAba3 (OXA-58-like; n = 2) and blaOXA-72 (OXA-24-like; n = 6). The isolates were classified into 21 pulsotypes using PFGE, and the representative 15 isolates were found to belong to sequence type ST2 of the Pasteur MLST scheme from the global IC2 clone. The Oxford MLST scheme revealed the diversity among these studied isolates, and identified five sequence types (ST195, ST208, ST208/ST1806, ST348 and ST425). CHDL-type carbapenemases and insertion elements upstream of the blaCHDL genes were found to be widespread among Polish A. baumannii clinical isolates, and this contributed to their carbapenem resistance.

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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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Study of the carbapenem resistance mechanisms in clinical isolates of Acinetobacter baumannii: Comparison of burn and non-burn strains

Burns ◽

10.1016/j.burns.2013.03.024 ◽

2013 ◽

Vol 39 (7) ◽

pp. 1414-1419 ◽

Cited By ~ 16

Author(s):

Omid Pajand ◽

Mohammad Ahangarzadeh Rezaee ◽

Mohammad Reza Nahaei ◽

Reza Mahdian ◽

Mohammad Aghazadeh ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Carbapenem Resistance ◽

Resistance Mechanisms ◽

Clinical Isolates

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

Antibiotics ◽

10.3390/antibiotics10030291 ◽

2021 ◽

Vol 10 (3) ◽

pp. 291

Author(s):

Paul G. Higgins ◽

Ralf Matthias Hagen ◽

Bernd Kreikemeyer ◽

Philipp Warnke ◽

Andreas Podbielski ◽

...

Keyword(s):

Middle East ◽

Acinetobacter Baumannii ◽

Resistance Genes ◽

Core Genome ◽

Carbapenem Resistance ◽

Resistance Mechanisms ◽

Northern Africa ◽

Carbapenem Resistant ◽

Next Generation Sequencing Ngs ◽

Injured Patients

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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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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Antimicrobial Resistance Mechanisms and Virulence of Colistin- and Carbapenem-Resistant Acinetobacter baumannii Isolated from a Teaching Hospital in Taiwan

Microorganisms ◽

10.3390/microorganisms9061295 ◽

2021 ◽

Vol 9 (6) ◽

pp. 1295

Author(s):

Noor Andryan Ilsan ◽

Yuarn-Jang Lee ◽

Shu-Chen Kuo ◽

I-Hui Lee ◽

Tzu-Wen Huang

Keyword(s):

Acinetobacter Baumannii ◽

Teaching Hospital ◽

Lipid A ◽

Signal Transduction Pathway ◽

Carbapenem Resistance ◽

Resistance Mechanisms ◽

Colistin Resistance ◽

Carbapenem Resistant ◽

Carbapenemase Gene ◽

Significant Difference

Acinetobacter baumannii, a Gram-negative bacterium, is an important nosocomial pathogen. Colistin-resistant A. baumannii is becoming a new concern, since colistin is one of the last-line antibiotics for infections by carbapenem-resistant A. baumannii. From 452 carbapenem-resistant isolates collected in a teaching hospital in Taipei, Taiwan, we identified seven that were resistant to colistin. Carbapenem resistance in these isolates is attributed to the presence of carbapenemase gene blaOXA-23 in their genomes. Colistin resistance is presumably conferred by mutations in the sensor kinase domain of PmrB found in these isolates, which are known to result in modification of colistin target lipid A via the PmrB–PmrA–PmrC signal transduction pathway. Overexpression of pmrC, eptA, and naxD was observed in all seven isolates. Colistin resistance mediated by pmrB mutations has never been reported in Taiwan. One of the seven isolates contained three mutations in lpxD and exhibited an altered lipopolysaccharide profile, which may contribute to its colistin resistance. No significant difference in growth rates was observed between the isolates and the reference strain, suggesting no fitness cost of colistin resistance. Biofilm formation abilities of the isolates were lower than that of the reference. Interestingly, one of the isolates was heteroresistant to colistin. Four of the isolates were significantly more virulent to wax moth larvae than the reference.

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PREVALENCE OF CARBAPENEM-RESISTANT ACINETOBACTER BAUMANNII (CRAB) IN MEDICAL AND SURGICAL INTENSIVE CARE UNITS (ICUS) OF JPMC, KARACHI

Pakistan Journal of Medicine and Dentistry ◽

10.36283/pjmd8-4/006 ◽

2019 ◽

Author(s):

Rabia Arshad

Keyword(s):

Intensive Care ◽

Antimicrobial Resistance ◽

Acinetobacter Baumannii ◽

Intensive Care Units ◽

Carbapenem Resistance ◽

Chronic Obstructive ◽

Surgical Intensive Care ◽

Carbapenem Resistant ◽

Number Of Patients ◽

Increased Risk

Background: Antimicrobial resistance is one of the research priorities of health organizations due to increased risk of morbidity and mortality. Outbreaks of nosocomial infections caused by carbapenem-resistant Acinetobacter Baumannii (CRAB) strains are at rise worldwide. Antimicrobial resistance to carbapenems reduces clinical therapeutic choices and frequently led to treatment failure. The aim of our study was to determine the prevalence of carbapenem resistance in A. baumannii isolated from patients in intensive care units (ICUs). Methods: This cross-sectional study was carried out in the Department of Microbiology, Basic Medical Sciences Institute (BMSI), Jinnah Postgraduate Medical Centre (JPMC), Karachi, from December 2016 to November 2017. Total 63 non-repetitive A. baumannii were collected from the patients’ specimens, admitted to medical and surgical ICUs and wards of JPMC, Karachi. The bacterial isolates were processed according to standard microbiological procedures to observe for carbapenem resistance. SPSS 21 was used for data analysis. Results: Out of the 63 patients, 40 (63.5%) were male. The age of the patient ranged from 15-85 year, with average of 43 year. 34.9% patients had been hospitalized for 3 days. Chronic obstructive pulmonary disease was present in highest number with average of 58.7% for morbidity. Number of patients on mechanical ventilation was highest (65.1%). All isolates were susceptible to colistin. The resistance to ampicillin-sulbactam, ceftazidime, ciprofloxacin, amikacin, piperacillin- tazobactam and meropenem was 82.5%, 81%, 100%, 87.3%, 82.5% and 82% respectively. Out of 82% CRAB, 77% were obtained from ICUs. Conclusion: This study has revealed the high rate of carbapenem resistance in A. baumannii isolates in ICUs thus leaving behind limited therapeutic options.

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Multicenter Clinical and Molecular Epidemiological Analysis of Bacteremia Due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE Epicenter of the United States

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02349-16 ◽

2017 ◽

Vol 61 (4) ◽

Cited By ~ 98

Author(s):

Michael J. Satlin ◽

Liang Chen ◽

Gopi Patel ◽

Angela Gomez-Simmonds ◽

Gregory Weston ◽

...

Keyword(s):

New York ◽

Empirical Therapy ◽

Carbapenem Resistance ◽

The United States ◽

Resistance Mechanisms ◽

Rapid Diagnostics ◽

Multicenter Studies ◽

Content Type ◽

Medical Centers ◽

Carbapenem Resistant

ABSTRACT Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among Enterobacteriaceae bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (cps), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation. The prevalences of carbapenem resistance among Klebsiella pneumoniae, Enterobacter spp., and Escherichia coli bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were K. pneumoniae and 92% produced K. pneumoniae carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing K. pneumoniae (KPC-Kp). The wzi154 allele, corresponding to cps-2, was present in 93% of KPC-3-Kp, whereas KPC-2-Kp had greater cps diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-Kp had an CAZ-AVI MIC of ≥4/4 μg/ml. There was a median of 47 h from bacteremia onset until active antimicrobial therapy, 38% of patients had septic shock, and 49% died within 30 days. KPC-3-Kp bacteremia (adjusted odds ratio [aOR], 2.58; P = 0.045), cancer (aOR, 3.61, P = 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79; P = 0.03) were independently associated with mortality. Active empirical therapy and combination therapy were not associated with survival. Despite a decade of experience with CRE, patients with CRE bacteremia have protracted delays in appropriate therapies and high mortality rates, highlighting the need for rapid diagnostics and evaluation of new therapeutics.

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