scholarly journals Clinical characteristics and outcomes of Pseudomonas aeruginosa bacteremia in febrile neutropenic children and adolescents with the impact of antibiotic resistance: a retrospective study

2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Hyo Sup Kim ◽  
Bo Kyoung Park ◽  
Seong koo Kim ◽  
Seung Beom Han ◽  
Jae Wook Lee ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Retrospective Study ◽  
Children And Adolescents ◽  
Clinical Characteristics ◽  
The Impact

scholarly journals Coexistence with Pseudomonas aeruginosa alters Staphylococcus aureus transcriptome, antibiotic resistance and internalization into epithelial cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Paul Briaud ◽  
Laura Camus ◽  
Sylvère Bastien ◽  
Anne Doléans-Jordheim ◽  
François Vandenesch ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Sequencing Analysis ◽  
Common Life ◽  
Transporter Family ◽  
Genes Encoding ◽  
Life Threatening ◽  
Internalization Rate ◽  
The Impact

Abstract Cystic fibrosis (CF) is the most common life-threatening genetic disease among Caucasians. CF patients suffer from chronic lung infections due to the presence of thick mucus, caused by cftr gene dysfunction. The two most commonly found bacteria in the mucus of CF patients are Staphylococcus aureus and Pseudomonas aeruginosa. It is well known that early-infecting P. aeruginosa strains produce anti-staphylococcal compounds and inhibit S. aureus growth. More recently, it has been shown that late-infecting P. aeruginosa strains develop commensal-like/coexistence interaction with S. aureus. The aim of this study was to decipher the impact of P. aeruginosa strains on S. aureus. RNA sequencing analysis showed 77 genes were specifically dysregulated in the context of competition and 140 genes in the context of coexistence in the presence of P. aeruginosa. In coexistence, genes encoding virulence factors and proteins involved in carbohydrates, lipids, nucleotides and amino acids metabolism were downregulated. On the contrary, several transporter family encoding genes were upregulated. In particular, several antibiotic pumps belonging to the Nor family were upregulated: tet38, norA and norC, leading to an increase in antibiotic resistance of S. aureus when exposed to tetracycline and ciprofloxacin and an enhanced internalization rate within epithelial pulmonary cells. This study shows that coexistence with P. aeruginosa affects the S. aureus transcriptome and virulence.

scholarly journals Characterization of Temporal Protein Production in Pseudomonas aeruginosa Biofilms

2005 ◽  
Vol 187 (23) ◽  
pp. 8114-8126 ◽  
Author(s):  
Christopher J. Southey-Pillig ◽  
David G. Davies ◽  
Karin Sauer
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Biofilm Formation ◽  
Protein Production ◽  
Developmental Stages ◽  
Developmental Process ◽  
Developmental Cycle ◽  
Specific Proteins ◽  
Biofilm Development ◽  
The Impact

ABSTRACT Phenotypic and genetic evidence supporting the notion of biofilm formation as a developmental process is growing. In the present work, we provide additional support for this hypothesis by identifying the onset of accumulation of biofilm-stage specific proteins during Pseudomonas aeruginosa biofilm maturation and by tracking the abundance of these proteins in planktonic and three biofilm developmental stages. The onset of protein production was found to correlate with the progression of biofilms in developmental stages. Protein identification revealed that proteins with similar function grouped within similar protein abundance patterns. Metabolic and housekeeping proteins were found to group within a pattern separate from virulence, antibiotic resistance, and quorum-sensing-related proteins. The latter were produced in a progressive manner, indicating that attendant features that are characteristic of biofilms such as antibiotic resistance and virulence may be part of the biofilm developmental process. Mutations in genes for selected proteins from several protein production patterns were made, and the impact of these mutations on biofilm development was evaluated. The proteins cytochrome c oxidase, a probable chemotaxis transducer, a two-component response regulator, and MexH were produced only in mature and late-stage biofilms. Mutations in the genes encoding these proteins did not confer defects in growth, initial attachment, early biofilm formation, or twitching motility but were observed to arrest biofilm development at the stage of cell cluster formation we call the maturation-1 stage. The results indicated that expression of theses genes was required for the progression of biofilms into three-dimensional structures on abiotic surfaces and the completion of the biofilm developmental cycle. Reverse transcription-PCR analysis confirmed the detectable change in expression of the respective genes ccoO, PA4101, and PA4208. We propose a possible mechanism for the role of these biofilm-specific proteins in biofilm formation.

scholarly journals Impact of AmpC Derepression on Fitness and Virulence: the Mechanism or the Pathway?

mBio ◽  
2016 ◽  
Vol 7 (5) ◽  
Author(s):  
Marcelo Pérez-Gallego ◽  
Gabriel Torrens ◽  
Jane Castillo-Vera ◽  
Bartolomé Moya ◽  
Laura Zamorano ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Cell Wall ◽  
Antibiotic Resistance ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Major Effect ◽  
Major Step ◽  
Alternative Pathways ◽  
The Impact ◽  
Cell Wall Recycling

ABSTRACTUnderstanding the interplay between antibiotic resistance and bacterial fitness and virulence is essential to guide individual treatments and improve global antibiotic policies. A paradigmatic example of a resistance mechanism is the intrinsic inducible chromosomal β-lactamase AmpC from multiple Gram-negative bacteria, includingPseudomonas aeruginosa, a major nosocomial pathogen. The regulation ofampCexpression is intimately linked to peptidoglycan recycling, and AmpC-mediated β-lactam resistance is frequently mediated by inactivating mutations inampD, encoding anN-acetyl-anhydromuramyl-l-alanine amidase, affecting the levels ofampC-activating muropeptides. Here we dissect the impact of the multiple pathways causing AmpC hyperproduction onP. aeruginosafitness and virulence. Through a detailed analysis, we demonstrate that the lack of all threeP. aeruginosaAmpD amidases causes a dramatic effect in fitness and pathogenicity, severely compromising growth rates, motility, and cytotoxicity; the latter effect is likely achieved by repressing key virulence factors, such as protease LasA, phospholipase C, or type III secretion system components. We also show thatampCoverexpression is required but not sufficient to confer the growth-motility-cytotoxicity impaired phenotype and that alternative pathways leading to similar levels ofampChyperexpression and resistance, such as those involving PBP4, had no fitness-virulence cost. Further analysis indicated that fitness-virulence impairment is caused by overexpressingampCin the absence of cell wall recycling, as reproduced by expressingampCfrom a plasmid in an AmpG (muropeptide permease)-deficient background. Thus, our findings represent a major step in the understanding of β-lactam resistance biology and its interplay with fitness and pathogenesis.IMPORTANCEUnderstanding the impact of antibiotic resistance mechanisms on bacterial pathogenesis is critical to curb the spread of antibiotic resistance. A particularly noteworthy antibiotic resistance mechanism is the β-lactamase AmpC, produced byPseudomonas aeruginosa, a major pathogen causing hospital-acquired infections. The regulation of AmpC is linked to the cell wall recycling pathways, and frequently, resistance to β-lactams is caused by mutation of several of the components of the cell wall recycling pathways such as AmpD. Here we dissect the impact of the pathways for AmpC hyperproduction on virulence, showing that the lack of all threeP. aeruginosaAmpD amidases causes a major effect in fitness and pathogenicity, compromising growth, motility, and cytotoxicity. Further analysis indicated that fitness-virulence impairment is specifically caused by the hyperproduction of AmpC in the absence of cell wall recycling. Our work provides valuable information for delineating future strategies for combatingP. aeruginosainfections by simultaneously targeting virulence and antibiotic resistance.

scholarly journals 2291. Evaluation of Multidrug-Resistant Pseudomonas aeruginosa Isolates in Patients Receiving Ceftolozane/tazobactam

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S785-S785
Author(s):  
Emily C Bodo ◽  
Aisling Caffrey ◽  
Vrishali Lopes ◽  
Jaclyn A Cusumano ◽  
Laura A Puzniak ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Retrospective Study ◽  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Veterans Affairs ◽  
Carbapenem Resistant ◽  
Clinical Culture ◽  
Resistance Rates ◽  
Lactamase Inhibitor

Abstract Background Multidrug-resistant (MDR) Pseudomonas aeruginosa is a challenging pathogen to treat. Ceftolozane/tazobactam (C/T) is a combination cephalosporin and β-lactamase inhibitor that has demonstrated activity against MDR P. aeruginosa, including carbapenem-resistant isolates. The objective of this study was to evaluate multidrug resistance in P. aeruginosa isolates obtained from patients treated with C/T across the Veterans Affairs (VA) Healthcare System nationally. Methods Hospitalized patients who received at least 1 dose of CT between January 2015 and April 2018 and had a positive P. aeruginosa culture were included in this retrospective study. Culture source and antimicrobial susceptibility reports were assessed for each P. aeruginosa isolate. Isolates were categorized as multidrug-resistant based on the Centers for Disease Control (CDC) definition. Resistance rates were categorized by source of culture. Results We identified 174 positive P. aeruginosa cultures among 154 patients who received at least one dose of C/T during the study period. The most common sources of isolates were lung (40% of patients), urine (21%), skin and soft tissue (15%), blood (14%), and bone/joint (14%). Most patients (98.1%) had isolates that were MDR, with high rates of carbapenem (84.4%), extended-spectrum cephalosporin (82.5%), and fluoroquinolone (79.9%) resistance. In this cohort, 50.6% of patients received at least one antibiotic prior to initiating C/T to which their clinical culture was not susceptible. Conclusion Antibiotic resistance was high in this cohort of patients with P. aeruginosa, and as a result, use of non-susceptible antibiotics occurred in 50.6% of patients before C/T was started. The high carbapenem resistance rates are of great clinical concern, but highlight an area of utilization for C/T given its activity against carbapenem-resistant P. aeruginosa. Disclosures All authors: No reported disclosures.

scholarly journals Learning from mistakes: analyzing incidents in a neonatal care unit

2019 ◽  
Vol 27 ◽  
Author(s):  
Louíse Viecili Hoffmeister ◽  
Gisela Maria Schebella Souto de Moura ◽  
Ana Paula Morais de Carvalho Macedo
Keyword(s):  
Retrospective Study ◽  
Health Professionals ◽  
Clinical Characteristics ◽  
Neonatal Care ◽  
Descriptive Statistics ◽  
Cross Sectional ◽  
Catheter Obstruction ◽  
Neonatal Care Unit ◽  
Perception Of Health ◽  
The Impact

ABSTRACT Objective: to analyze incidents reported in a neonatal care unit. Method: a quantitative, cross-sectional and retrospective study with a sample of 34 newborns. Data were collected through a structured form, composed of two parts: sociodemographic/clinical characteristics of the newborns, and characteristics of the reported incidents. Data were collected from the institution’s computer system, in a period corresponding to 13 months, and analyzed by means of descriptive statistics. Results: the majority of the newborns were preterm (70.6%), male (52.9%) and born through caesarean section (76.5%). During the study period, 54 incidents were reported, totaling a frequency of 1.6 incident per newborn. It was found that 61.1% of incidents were related to medicines, 14.8% to accidental loss of tracheal tube and 9.3% to catheter obstruction. Conclusion: analysis of the reported incidents has shown that most incidents refer to the drug process. Information about the incidents can increase the perception of health professionals regarding the impact of their actions.

scholarly journals The high persister phenotype ofPseudomonas aeruginosais associated with increased fitness and persistence in cystic fibrosis airways

2019 ◽  
Author(s):  
Biljana Mojsoska ◽  
David R. Cameron ◽  
Jennifer A. Bartell ◽  
Janus Anders Juul Haagensen ◽  
Lea M. Sommer ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Genetic Alterations ◽  
Antibiotic Tolerance ◽  
High Throughput Screening Assay ◽  
The Impact ◽  
Over Time ◽  
Better Than

AbstractDespite intensive antibiotic treatment of cystic fibrosis (CF) patients,Pseudomonas aeruginosaoften persists in patient airways for decades, and can do so without the development of antibiotic resistance. Using a high-throughput screening assay of survival after treatment with high concentrations of ciprofloxacin, we have determined the prevalence of high-persister variants (Hip) in a large patient cohort. In a screen of 467 longitudinal clinical isolates ofP. aeruginosafrom 40 CF patients, we classified 25.7% as Hip. Hip were identified in 26 patients, but only a few bacterial lineages were dominated by Hip. Instead, the emergence of Hip increased over time, suggesting that CF airways treated with ciprofloxacin select for Hip with an increased fitness in this environment. We generally observed diverse genetic changes in the Hip isolate population (as many co-occurring routes to increased fitness exist), but interestingly elevated mutation counts in the RpoN gene of 18 Hip isolates suggest that this sigma factor plays a role in shaping levels of antibiotic tolerance. To probe the impact of the Hip phenotype in a CF-similar environment, we tested the fitness properties of otherwise genotypically and phenotypically similar low-persister (Lop) and Hip isolates in co-culture using a specialized flow-cell biofilm system mimicking pharmacokinetic/-dynamic antibiotic dosing. Hip survived ciprofloxacin treatment far better than Lop isolates. The results of this investigation provide novel insights into persister dynamics and fitness contributions to survival in the CF lung, and show that the Hip phenotype of antibiotic susceptible bacteria plays an important role in long-term infections.SignificanceAntibiotic resistance is emphasized as a rapidly increasing health threat, but antibiotic tolerance via the occurrence of persister cells in antibiotic-treated bacterial populations is clinically and publicly neglected. In 40 CF patients representing a well-established human infection model – long-term lung infections byPseudomonas aeruginosa– we show the emergence and accumulation of persister variants in a clinical population heavily reliant on antibiotic therapy. We observe that the high-persister (Hip) phenotype is independent of resistance and likely the consequence of numerous genetic alterations, complicating surveillance and inhibition in the clinic. Furthermore, we find Hip are selected for over time, survive better than ‘normal’ bacteria, and can outcompete them in CF-similar conditions, ultimately affecting 65% of patients in an early disease cohort.

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