scholarly journals Molecular epidemiology of multidrug-resistant Acinetobacter baumannii infection in two hospitals in Central Brazil: the role of ST730 and ST162 in clinical outcomes

2019 ◽  
Vol 68 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Francisco Kennedy S. F. de Azevedo ◽  
Valéria Dutra ◽  
Luciano Nakazato ◽  
Camila Martines Mello ◽  
Marco Andrey Pepato ◽  
...  
Keyword(s):  
Molecular Epidemiology ◽  
Acinetobacter Baumannii ◽  
Clinical Outcomes ◽  
Multidrug Resistant ◽  
Central Brazil

Treatment, clinical outcomes, and predictors of mortality among a national cohort of admitted patients with Acinetobacter baumannii infection

2022 ◽  
Author(s):  
Haley J. Appaneal ◽  
Vrishali V. Lopes ◽  
Kerry L. LaPlante ◽  
Aisling R. Caffrey
Keyword(s):  
Acinetobacter Baumannii ◽  
Clinical Outcomes ◽  
Healthcare Providers ◽  
Multidrug Resistant ◽  
Inpatient Mortality ◽  
Logistic Regression Models ◽  
Predictors Of Mortality ◽  
Risk Of Death ◽  
National Cohort ◽  
Infectious Source

Objectives: To analyze treatment, clinical outcomes, and predictors of mortality in hospitalized patients with Acinetobacter baumannii infection. Methods: Retrospective cohort study of inpatients with A. baumannii cultures and treatment from 2010-2019. Patients who died during admission were compared to those who survived to identify predictors of inpatient mortality, using multivariable unconditional logistic regression models. Results: We identified 4,599 inpatients with A. baumannii infection; 13.6% died during admission. Fluoroquinolones (26.8%), piperacillin/tazobactam (24%) and carbapenems (15.6%) were used for treatment. Tigecycline (3%) and polymyxins (3.7%) were not used often. Predictors of inpatient mortality included current acute respiratory failure (adjusted odds ratio [aOR] 3.94), shock (aOR 3.05), and acute renal failure (aOR 2.01); blood (aOR 1.94) and respiratory (aOR 1.64) infectious source; multidrug-resistant A. baumannii (MDRAB) infection (aOR 1.66); liver disease (aOR 2.15); and inadequate initial treatment (aOR 1.30). Inpatient mortality was higher in those with MDRAB vs. non-MDRAB (aOR 1.61) and in those with CRAB vs. non-CRAB infection (aOR 1.68). Length of stay >10 days was higher among those with MDRAB vs. non-MDRAB (aOR 1.25) and in those with CRAB vs. non-CRAB infection (aOR 1.31). Conclusions: In our national cohort of inpatients with A. baumannii infection, clinical outcomes were worse among those with MDRAB and/or CRAB infection. Predictors of inpatient mortality included several current conditions associated with severity, infectious source, underlying illness, and inappropriate treatment. Our study may assist healthcare providers in the early identification of admitted patients with A. baumannii infection who are at higher risk of death.

scholarly journals Colistin heteroresistance and the involvement of the PmrAB regulatory system in Acinetobacter baumannii

2018 ◽  
Author(s):  
Yannick Charretier ◽  
Seydina M. Diene ◽  
Damien Baud ◽  
Sonia Chatellier ◽  
Emmanuelle Santiago-Allexant ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Population Analysis ◽  
Regulatory System ◽  
Clinical Problem ◽  
Multidrug Resistant ◽  
Regulatory Pathway ◽  
Colistin Resistance ◽  
Bacterial Killing ◽  
One Step

AbstractMultidrug-resistant Acinetobacter baumannii infection has recently emerged as a worldwide clinical problem and colistin is increasingly being used as last resort therapy. Despite its favorable bacterial killing, resistance and heteroresistance to colistin have been described. Mutations in the PmrAB regulatory pathway have been already associated with colistin resistance whereas the mechanisms for heteroresistance remain largely unknown. The purpose of the present study is to investigate the role of PmrAB in laboratory-selected mutants representative of global epidemic strains. During brief colistin exposure, colistin resistant and colistin heteroresistant mutants were selected in a one-step strategy. Population Analysis Profiling (PAP) was performed to confirm the suspected phenotype. Upon withdrawal of selective pressure, compensatory mutations were evaluated in another one-step strategy. A trans-complementation assay was designed to delineate the involvement of the PmrAB regulatory system using qPCR and PAP. Mutations in the PmrAB regulatory pathway were associated with colistin resistance and colistin heteroresistance as well. The transcomplementation assay provides a proof for the role played by changes in the PmrAB regulatory pathway. The level of colistin resistance is correlated to the level of expression of pmrC. The resistance phenotype was partially restored since the complemented strain became heteroresistant. This report shows the role of different mutations in the PmrAB regulatory pathway and warns on the development of colistin heteroresistance that could be present but not easily detected with routine testing.

scholarly journals Characterization of RelA in Acinetobacter baumannii

2020 ◽  
Vol 202 (12) ◽  
Author(s):  
María Pérez-Varela ◽  
Aimee R. P. Tierney ◽  
Ju-Sim Kim ◽  
Andrés Vázquez-Torres ◽  
Philip Rather
Keyword(s):  
Acinetobacter Baumannii ◽  
Galleria Mellonella ◽  
Multidrug Resistant ◽  
Cell Physiology ◽  
Content Type ◽  
Content Model ◽  
Transposon Insertion ◽  
Downstream Effectors

ABSTRACT In response to nutrient depletion, the RelA and SpoT proteins generate the signaling molecule (p)ppGpp, which then controls a number of downstream effectors to modulate cell physiology. In Acinetobacter baumannii strain AB5075, a relA ortholog (ABUW_3302) was identified by a transposon insertion that conferred an unusual colony phenotype. An in-frame deletion in relA (ΔrelA) failed to produce detectable levels of ppGpp when amino acid starvation was induced with serine hydroxamate. The ΔrelA mutant was blocked from switching from the virulent opaque colony variant (VIR-O) to the avirulent translucent colony variant (AV-T), but the rate of AV-T to VIR-O switching was unchanged. In addition, the ΔrelA mutation resulted in a pronounced hypermotile phenotype on 0.35% agar plates. This hypermotility was dependent on the activation of a LysR regulator ABUW_1132, which was required for expression of AbaR, a LuxR family quorum-sensing regulator. In the ΔrelA mutant, ABUW_1132 was also required for the increased expression of an operon composed of the ABUW_3766-ABUW_3773 genes required for production of the surfactant-like lipopeptide acinetin 505. Additional phenotypes identified in the ΔrelA mutant included (i) cell elongation at high density, (ii) reduced formation of persister cells tolerant to colistin and rifampin, and (iii) decreased virulence in a Galleria mellonella model. IMPORTANCE Acinetobacter baumannii is a pathogen of worldwide importance. Due to the increasing prevalence of antibiotic resistance, these infections are becoming increasingly difficult to treat. New therapies are required to combat multidrug-resistant isolates. The role of RelA in A. baumannii is largely unknown. This study demonstrates that like in other bacteria, RelA controls a variety of functions, including virulence. Strategies to inhibit the activity of RelA and the resulting production of ppGpp could inhibit virulence and may represent a new therapeutic approach.

scholarly journals Multidrug resistant Acinetobacter baumannii--the role of AdeABC (RND family) efflux pump in resistance to antibiotics.

2008 ◽  
Vol 46 (3) ◽  
Author(s):  
Piotr Wieczorek ◽  
Paweł Sacha ◽  
Tomasz Hauschild ◽  
Marcin Zórawski ◽  
Małgorzata Krawczyk ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Resistance To Antibiotics

scholarly journals In-Depth Analysis of the Role of the Acinetobactin Cluster in the Virulence of Acinetobacter baumannii

2021 ◽  
Vol 12 ◽  
Author(s):  
Kelly Conde-Pérez ◽  
Juan C. Vázquez-Ucha ◽  
Laura Álvarez-Fraga ◽  
Lucía Ageitos ◽  
Soraya Rumbo-Feal ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Multidrug Resistant ◽  
Significant Loss ◽  
Genetic Redundancy ◽  
Double Mutant Strain ◽  
Wide Range ◽  
Depth Analysis ◽  
High Level ◽  
Antivirulence Agents

Acinetobacter baumannii is a multidrug-resistant pathogen that represents a serious threat to global health. A. baumannii possesses a wide range of virulence factors that contribute to the bacterial pathogenicity. Among them, the siderophore acinetobactin is one of the most important, being essential for the development of the infection. In this study we performed an in-depth analysis of the acinetobactin cluster in the strain A. baumannii ATCC 17978. For this purpose, nineteen individual isogenic mutant strains were generated, and further phenotypical analysis were performed. Individual mutants lacking the biosynthetic genes entA, basG, basC, basD, and basB showed a significant loss in virulence, due to the disruption in the acinetobactin production. Similarly, the gene bauA, coding for the acinetobactin receptor, was also found to be crucial for the bacterial pathogenesis. In addition, the analysis of the ΔbasJ/ΔfbsB double mutant strain demonstrated the high level of genetic redundancy between siderophores where the role of specific genes of the acinetobactin cluster can be fulfilled by their fimsbactin redundant genes. Overall, this study highlights the essential role of entA, basG, basC, basD, basB and bauA in the pathogenicity of A. baumannii and provides potential therapeutic targets for the design of new antivirulence agents against this microorganism.

scholarly journals Effect of frameshift mutagen acriflavine on control of resistance genes in Acinetobacter baumannii

2011 ◽  
Vol 60 (2) ◽  
pp. 211-215 ◽  
Author(s):  
B. S. Lopes ◽  
A. Hamouda ◽  
J. Findlay ◽  
S. G. B. Amyes
Keyword(s):  
Gene Expression ◽  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Resistance Genes ◽  
Outer Membrane Proteins ◽  
Antibiotic Resistance Gene ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
The Body

Acinetobacter baumannii is a Gram-negative pathogenic bacterium that often exhibits a multidrug-resistant phenotype causing infections at various sites of the body and increasingly leading to septicaemic shock. This study evaluated the role of acriflavine, a frameshift mutagen, on the movement of insertion sequence ISAba1 in clinical isolates of A. baumannii, with the focus on changes in expression levels of the bla ADC and bla OXA-51-like genes. Resistance profiles were assessed with consideration of ISAba1 acting as a promoter upstream of the bla ADC or bla OXA-51-like gene. ISAba1 movement was observed in the acriflavine mutants Ab153M and Ab1225M. Ab153M exhibited an increase in the MIC values of carbapenems and ceftazidime, with ISAba1 gained upstream of the bla ADC and bla OXA-51-like genes, correlating with an increase in gene expression. Reduced expression of the 17, 23 and 25 kDa outer-membrane proteins (OMPs) was also observed in Ab153M. There was a significant decrease in MIC values of carbapenems with the loss of ISAba1 upstream of the bla ADC and bla OXA-51-like genes in strain Ab1225M, and a significant decrease in bla OXA-51-like gene expression and, to a lesser extent, in bla ADC expression. Ab1225M and a serially subcultured Ab1225 strain (Ab1225s) exhibited overexpression of the 17, 23, 25 and 27 kDa OMPs. There was a decrease in MIC values of the carbapenems and piperacillin/tazobactam but not of ceftazidime in Ab1225s, which had ISAba1 upstream of the bla ADC and bla OXA-51-like genes. A significant decrease in bla OXA-51-like expression was observed in Ab1225s, whereas the expression of bla ADC was similar to that in the Ab1225 parental strain. The attenuation in this strain may be due to overexpression of OMPs and it is clear that, even if ISAba1 is present upstream of an antibiotic resistance gene, it may not necessarily contribute towards the overexpression of antibiotic resistance genes (bla OXA-51-like in Ab1225s). Movement of the IS element within the A. baumannii chromosome may be an important regulatory mechanism employed by the bacterium under particular stress conditions, and the ability to upregulate the expression of antibiotic resistance genes is likely to be an important factor in the pathogenicity of this bacterium.

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