Synergistic activities between carbapenems and other antimicrobial agents against Acinetobacter baumannii including multidrug-resistant and extensively drug-resistant isolates

2010 ◽  
Vol 36 (3) ◽  
pp. 243-246 ◽  
Author(s):  
Pattarachai Kiratisin ◽  
Anucha Apisarnthanarak ◽  
Srirumpa Kaewdaeng
Keyword(s):  
Acinetobacter Baumannii ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Extensively Drug Resistant

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.

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.

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 Antimicrobial activity of a repurposed harmine-derived compound on extensively drug-resistant Acinetobacter baumannii clinical isolates

2021 ◽  
Author(s):  
Anke Breine ◽  
Megane Van Gysel ◽  
Mathias Elsocht ◽  
Clemence Whiteway ◽  
Chantal Philippe ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Reference Strain ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Antibiotic Resistant ◽  
Carbapenem Resistant ◽  
Extensively Drug Resistant ◽  
Resistant Strains ◽  
High Degree

Synopsis Objectives: The spread of antibiotic resistant bacteria is an important threat for human healthcare. Acinetobacter baumannii bacteria impose one of the major issues, as multidrug- to pandrug-resistant strains have been found, rendering some infections untreatable. In addition, A. baumannii is a champion in surviving in harsh environments, being capable of resisting to disinfectants and to persist prolonged periods of desiccation. Due to the high degree of variability found in A. baumannii isolates, the search for new antibacterials is challenging. Here, we screened a compound library to identify compounds active against recent isolates of A. baumannii bacteria. Methods: A repurposing drug screen was undertaken to identify A. baumannii growth inhibitors. One hit was further characterized by determining its IC50 and testing its activity on 43 recent clinical A. baumannii isolates, amongst which 40 are extensively drug- and carbapenem-resistant strains. Results: The repurposing screen led to the identification of a harmine-derived compound, called HDC1, which proved to have bactericidal activity on the multidrug-resistant AB5075-VUB reference strain with an IC50 of 48.23 [mu]M. In addition, HDC1 impairs growth of all 43 recent clinical A. baumannii isolates. Conclusions: We identified a compound with inhibitory activity on all tested, extensively drug-resistant clinical A. baumannii isolates.

Retrospective analysis of the emergence of antibiotic-resistant Salmonella enterica infections in a level IV hospital from Lima, Peru

2021 ◽  
pp. 004947552110609
Author(s):  
Joaquim Ruiz ◽  
Wilfredo Flores-Paredes ◽  
Nestor Luque ◽  
Roger Albornoz ◽  
Nayade Rojas ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Hospitalized Patients ◽  
Drug Resistant ◽  
Antibiotic Resistant ◽  
Salmonella Infections ◽  
Extensively Drug Resistant ◽  
Period 2 ◽  
Automated Methods

This study retrospectively analysed the emergence of multidrug-resistant Salmonella enterica in a level IV hospital in Lima, Peru. A total of 64 S. enterica from January 2009 to June 2010 (Period 1, 24 isolates) and January 2012 to December 2014 (Period 2, 40 isolates) were included. Some 25 were from non-hospitalized and 39 from hospitalized patients. Antimicrobial susceptibility to 15 antimicrobial agents was established by automated methods. Most of the isolates were from blood (46.9%), urine (21.9%) and faeces (14.1%). There was a reduction in blood isolates in Period 2, while all the faecal isolates were from this period. In Period 1, only 3/24 (12.5%) isolates showed antibiotic resistance, whereas 25/39 isolates (64.1%) from Period 2 were antibiotic-resistant, with multidrug-resistant and extensively drug-resistant rates of 17.9% and 20.5%, respectively. Multidrug-resistant/extensively drug-resistant Salmonella isolates were introduced in the hospital in 2013, with Salmonella recovered from faeces from non-hospitalized patients suggested an increase in community-acquired multidrug-resistant/extensively drug-resistant Salmonella infections.

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