scholarly journals Carbapenemases: Transforming Acinetobacter baumannii into a Yet More Dangerous Menace

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 720 ◽  
Author(s):  
Maria Soledad Ramirez ◽  
Robert A. Bonomo ◽  
Marcelo E. Tolmasky
Keyword(s):  
Acinetobacter Baumannii ◽  
Nosocomial Infections ◽  
Acquired Resistance ◽  
Clinical Manifestations ◽  
High Capacity ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Wound Infections ◽  
Extensively Drug Resistant

Acinetobacter baumannii is a common cause of serious nosocomial infections. Although community-acquired infections are observed, the vast majority occur in people with preexisting comorbidities. A. baumannii emerged as a problematic pathogen in the 1980s when an increase in virulence, difficulty in treatment due to drug resistance, and opportunities for infection turned it into one of the most important threats to human health. Some of the clinical manifestations of A. baumannii nosocomial infection are pneumonia; bloodstream infections; lower respiratory tract, urinary tract, and wound infections; burn infections; skin and soft tissue infections (including necrotizing fasciitis); meningitis; osteomyelitis; and endocarditis. A. baumannii has an extraordinary genetic plasticity that results in a high capacity to acquire antimicrobial resistance traits. In particular, acquisition of resistance to carbapenems, which are among the antimicrobials of last resort for treatment of multidrug infections, is increasing among A. baumannii strains compounding the problem of nosocomial infections caused by this pathogen. It is not uncommon to find multidrug-resistant (MDR, resistance to at least three classes of antimicrobials), extensively drug-resistant (XDR, MDR plus resistance to carbapenems), and pan-drug-resistant (PDR, XDR plus resistance to polymyxins) nosocomial isolates that are hard to treat with the currently available drugs. In this article we review the acquired resistance to carbapenems by A. baumannii. We describe the enzymes within the OXA, NDM, VIM, IMP, and KPC groups of carbapenemases and the coding genes found in A. baumannii clinical isolates.

scholarly journals Multidrug resistant and extensively drug resistant Acinetobacter baumannii hospital infection associated with high mortality: A retrospective study in the Pediatric Intensive Care Unit

2020 ◽  
Author(s):  
Jingyi Shi ◽  
Ting Sun ◽  
Yun Cui ◽  
Chunxia Wang ◽  
Fei Wang ◽  
...  
Keyword(s):  
Serum Level ◽  
Acinetobacter Baumannii ◽  
High Mortality ◽  
Pediatric Intensive Care ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
High Serum ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Overall Mortality

Abstract Background Multidrug resistant (MDR) and extensively drug resistant (XDR) Acinetobacter baumannii presents challenges for clinical treatment and causes high mortality in children. We aimed to assess the risk factors for MDR/XDR Acinetobacter baumannii infection and for overall mortality in this patient population. Methods This retrospective study included 102 pediatric patients who developed MDR/XDR Acinetobacter baumannii infection in the pediatric intensive care unit (PICU) of Shanghai Children’s Hospital in China from December 2014 to May 2018. Clinical presentations and outcome of the patients were analyzed. The primary outcome was overall mortality. Secondary outcomes included the 28-day mortality and the length of hospital stay. Results Of the 102 patients (63 males and 39 females; mean age: 51.79 months), the overall mortality rate was 29.41%. 18(17.64%) had bloodstream infections;4(3.92%) for which cerebrospinal fluid (CSF) cultures were positive; 14(13.73%) of them got positive cultures in aseptic fluid; 10 (9.8%) had central catheter-associated bloodstream infections; lower respiratory isolates (56/102) accounted for 54.9% of all patients. Non-survival patients appeared to have a lower NK cell activity 5.87%(2.43%, 8.93%) vs. 8.45%(4.51%, 14.61%), P =0.011), higher CD4 + T cell ratio (35.32% (29%, 47.81%) vs. 31.97% (20.52%, 38.22%), P = 0.045), and higher serum level of interlukin-6 (IL-6, 235.51(0.1, 4172.77) pg/ml vs. 0.1(0.1, 110.92) pg/ml, P = 0.028), interlukin-8 (IL-8, 22.73(3.14, 540.12) vs. 0.1(0.1, 25.85)pg/ml, P = 0.03) , and interlukin-10(10.82(0.1, 83.29)pg/ml vs. 6.05(0.1,21.81)pg/ml) were observed. Multivariate logistic analysis indicated that high serum level of BUN (RR, 1.216, 95%CI, 1.27-2.616; P = 0.001) and high serum level of Cr (RR, 1.823, 95%CI, 0.902-0.980；P=0.004,) were associated with high risk of overall mortality in MDR/XDR Acinetobacter baumannii infected patients. Conclusion MDR/XDR- Acinetobacter baumannii is an important opportunistic pathogen that causes nosocomial infection in PICU with a rather high mortality. The incidence increased in recent years, ineffective management, immune dysfunction, acute kidney injury contributed to the risk of death.

scholarly journals Epidemiology and Genetic Diversity of Colistin Nonsusceptible Nosocomial Acinetobacter baumannii Strains from Russia for 2013-2014

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Eugene A. Sheck ◽  
Mikhail V. Edelstein ◽  
Marina V. Sukhorukova ◽  
Natali V. Ivanchik ◽  
Elena Yu. Skleenova ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Nosocomial Infections ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Epidemiological Features ◽  
High Level ◽  
Therapeutic Possibilities

A high level of resistance to carbapenems in Acinetobacter baumannii strains severely limits therapeutic possibilities. Colistin is the last resort drug against such strains, although the cases of resistance to this drug have become more frequent. This article presents the epidemiological features and genetic diversity of colistin nonsusceptible A. baumannii strains collected as part of a national multicenter epidemiological study of the antibiotic resistance of pathogens of nosocomial infections (MARATHON), which was conducted in 2013-2014 in Russia. A total of 527 A. baumannii isolates were collected, 10 (1.9%) of which were nonsusceptible to colistin. The majority of nonsusceptible A. baumannii isolates to colistin showed resistance to carbapenems and had the genes of the acquired OXA-40-like carbapenemases (n=6). In one case, a combination of OXA-23-like + OXA-40-like (n=1) genes was identified. One strain had the multidrug-resistant (MDR) phenotype, 6 isolates had extensively drug-resistant (XDR) phenotype, and 3 isolates had pandrug-resistant (PDR) phenotype. Among the colistin nonsusceptible A. baumannii isolates, 6 individual genotypes were identified, most of which belonged to successful international clones (CC92OXF/CC2PAS, n=4; CC944OXF/ST78PAS, n=4; CC109OXF/CC1PAS, n=1).

Extensively drug-resistant Acinetobacter baumannii nosocomial pneumonia successfully treated with a novel antibiotic combination

2021 ◽  
Author(s):  
Noor Zaidan ◽  
J. Patrik Hornak ◽  
David Reynoso
Keyword(s):  
Septic Shock ◽  
Drug Development ◽  
Acinetobacter Baumannii ◽  
Nosocomial Infections ◽  
Drug Resistant ◽  
Access Protocol ◽  
The Poor ◽  
Extensively Drug Resistant ◽  
Poor Outcomes ◽  
Antibiotic Combination

Extremely drug resistant (XDR) Acinetobacter baumannii cause challenging nosocomial infections. We report the case of a patient with XDR A. baumannii pneumonia and septic shock successfully treated with cefiderocol and a novel antibiotic obtained via expanded access protocol. With focused research and drug development efforts, the poor outcomes associated with these infections may be mitigated.

Whole genome analysis of extensively drug-resistant Acinetobacter bau-mannii clinical isolates in Thailand

2020 ◽  
Vol 20 ◽  
Author(s):  
Peechanika Chopjitt ◽  
Anusak Kerdsin ◽  
Dan Takeuchi ◽  
Rujirat Hatrongjit ◽  
Parichart Boueroy ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Acinetobacter Baumannii ◽  
Genome Sequencing ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Whole Genome ◽  
Drug Resistant ◽  
Resistant Genes ◽  
Extensively Drug Resistant ◽  
Antibiotic Efflux

Background:: Acinetobacter baumannii is recognized as a majority opportunistic nosocomial pathogen and caus-ing hospital-acquired infection worldwide. The increasing prevalence of extensively drug-resistant Acinetobacter baumannii (XDRAB) has become a rising concern in healthcare facilities and has impeded public health due to limitation of therapeutic options and are associated with high morbidity and mortality as well as longer hospitalization. Whole-genome sequencing of highly multidrug resistant A. baumannii will increase understanding of resistant mechanisms, the emergence of novel re-sistance, genetic relationships among the isolates, source tracking, and treatment decisions in selected patients. Objective:: This study revealed the genomic analysis to explore blaOXA-23 harboring XDRAB isolates in Thailand. Methods:: Whole-genome sequencing of the two XDRAB isolates was carried out on a HiSeq2000 Illumina platform and susceptibility on antimicrobials was conducted. Results:: Both isolates revealed sequence types of international, clone II-carrying, multiple antimicrobial-resistant genes—ST195 and ST451. They were resistant to antimicrobial agents in all drug classes tested for Acinetobacter spp. They carried 18 antimicrobial-resistant genes comprising of 4 -lactamase genes (blaOXA-23, blaOXA-66, blaTEM-1D, blaADC-25), 4 aminogly-coside-resistant genes (armA, aph(3')-Ia, aph(3'')-Ib, aph(6)-Id), 3 macrolide-resistant genes (amvA, mphE, msrE), 1 sulfon-amide-resistant gene (sul-2), 2 tetracycline-resistant genes (tetB, tetR), 1 resistant-nodulation-cell division (RND) antibiotic efflux pump gene cluster, 2 major facilitator superfamily (MFS) antibiotic efflux pump genes (abaF, abaQ), and 1 small multidrug-resistant (SMR) antibiotic efflux pump gene (abeS). Mutation of gyrA (S81L) occurred in both isolates. Conclusions:: Whole-genome sequencing revealed both blaOXA-23 harboring XDRAB isolates were clustered under interna-tional clone II with difference STs and carrying multiple antimicrobial-resistant genes conferred their resistance to antimi-crobial agents. Inactivation of antimicrobials and target modification by enzymes, and pumping antibiotics by efflux pump are mainly resistance mechanism of the XDRAB in this study.

scholarly journals Selectable Markers for Use in Genetic Manipulation of Extensively Drug-Resistant (XDR) Acinetobacter baumannii HUMC1

mSphere ◽  
2017 ◽  
Vol 2 (2) ◽  
Author(s):  
Brian M. Luna ◽  
Amber Ulhaq ◽  
Jun Yan ◽  
Paul Pantapalangkoor ◽  
Travis B. Nielsen ◽  
...  
Keyword(s):  
Molecular Biology ◽  
Acinetobacter Baumannii ◽  
Genetic Manipulation ◽  
Multidrug Resistant ◽  
Molecular Techniques ◽  
Drug Resistant ◽  
Selectable Markers ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Selection Of

ABSTRACT Multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) strains of Acinetobacter baumannii have frequently been characterized. The ability of A. baumannii to develop resistance to antibiotics is a key reason this organism has been difficult to study using genetic and molecular biology approaches. Here we report selectable markers that are not only useful but necessary for the selection of drug-resistant transformants in the setting of drug-resistant backgrounds. Use of these selectable markers can be applied to a variety of genetic and molecular techniques such as mutagenesis and transformation. These selectable markers will help promote genetic and molecular biology studies of otherwise onerous drug-resistant strains, while avoiding the generation of pathogenic organisms that are resistant to clinically relevant antibiotics. Acinetobacter baumannii is one of the most antibiotic-resistant pathogens in clinical medicine, and extensively drug-resistant (XDR) strains are commonly isolated from infected patients. Such XDR strains are already resistant to traditional selectable genetic markers, limiting the ability to conduct pathogenesis research by genetic disruption. Optimization of selectable markers is therefore critical for the advancement of fundamental molecular biology techniques to use in these strains. We screened 23 drugs that constitute a broad array of antibiotics spanning multiple drug classes against HUMC1, a highly virulent and XDR A. baumannii clinical blood and lung isolate. HUMC1 is resistant to all clinically useful antibiotics that are reported by the clinical microbiology laboratory, except for colistin. Ethical concerns about intentionally establishing pan-resistance, including to the last-line agent, colistin, in a clinical isolate made identification of other markers desirable. We screened additional antibiotics that are in clinical use and those that are useful only in a lab setting to identify selectable markers that were effective at selecting for transformants in vitro. We show that supraphysiological levels of tetracycline can overcome innate drug resistance displayed by this XDR strain. Last, we demonstrate that transformation of the tetA (tetracycline resistance) and Sh ble (zeocin resistance), but not pac (puromycin resistance), resistance cassettes allow for selection of drug-resistant transformants. These results make the genetic manipulation of XDR A. baumannii strains easily achieved. IMPORTANCE Multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) strains of Acinetobacter baumannii have frequently been characterized. The ability of A. baumannii to develop resistance to antibiotics is a key reason this organism has been difficult to study using genetic and molecular biology approaches. Here we report selectable markers that are not only useful but necessary for the selection of drug-resistant transformants in the setting of drug-resistant backgrounds. Use of these selectable markers can be applied to a variety of genetic and molecular techniques such as mutagenesis and transformation. These selectable markers will help promote genetic and molecular biology studies of otherwise onerous drug-resistant strains, while avoiding the generation of pathogenic organisms that are resistant to clinically relevant antibiotics.

Successful Treatment of Antibiotic-resistant, Poly-microbial Bone Infection With Bacteriophages and Antibiotics Combination

2019 ◽  
Vol 69 (11) ◽  
pp. 2015-2018 ◽  
Author(s):  
Ran Nir-Paz ◽  
Daniel Gelman ◽  
Ayman Khouri ◽  
Brittany M Sisson ◽  
Joseph Fackler ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Acinetobacter Baumannii ◽  
Successful Treatment ◽  
Positive Culture ◽  
Multidrug Resistant ◽  
Bone Infection ◽  
Drug Resistant ◽  
Antibiotic Resistant ◽  
Extensively Drug Resistant ◽  
Tissue Healing

Abstract A patient with a trauma-related left tibial infection associated with extensively drug-resistant Acinetobacter baumannii and multidrug-resistant Klebsiella pneumoniae was treated with bacteriophages and antibiotics. There was rapid tissue healing and positive culture eradication. As a result, the patient’s leg did not have to be amputated and he is undergoing rehabilitation.

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