scholarly journals PROBLEMS OF THE TREATMENT OF PNEUMONIA CAUSED BY PSEUDOMONAS AERUGINOSA

2019 ◽  
Vol 42 (3) ◽  
pp. 78-83
Author(s):  
Mochonyi V. A. ◽  
Savchenko O. A. ◽  
Podsevakhina S. L. ◽  
Tkachenko O. V.
Keyword(s):  
Risk Factors ◽  
Pseudomonas Aeruginosa ◽  
Synergistic Effect ◽  
Poor Prognosis ◽  
Acquired Resistance ◽  
Severe Pneumonia ◽  
Natural Resistance ◽  
Beta Lactams ◽  
Pseudomonas Infection ◽  
High Level

Pseudomonas infection is one of the most problematic pathogens of pneumonia, because it has natural resistance to many antibiotics, is able to quickly form acquired resistance, often causes severe pneumonia with a poor prognosis. Analysis of the literature data showed that today P. Aeruginosa demonstrates resistance to all anti-pest control antibiotics, with the exception of polymyxin. The levels of resistance of P.Aeruginosa are very considerably depending on the region of the survey and the profile of the hospital, which requires monitoring the sensitivity of microorganisms in each department of the hospital. The data on the degree of resistance to P. Aeruginosa antibiotics in Ukraine are limited, but available local studies on this issue also show a high level of resistance of this microorganism to the main anti-pest antibiotics. In patients with pneumonia and risk factors for the involvement of Pseudomonas infection, most authors recommend combination antibiotic therapy, which has a synergistic effect on P. Aeruginosa, which allows, in most cases, to overcome the resistance of this microorganism. According to the literature, such synergism has been proven for the combination: beta-lactams (ceftazidime, cefepime, antipseudomonas carbapenems) + aminoglycosides (amikacin) or fluoroquinolones (ciprofloxacin or levofloxacin). The use of these drugs in the maximum allowable dose allows a higher degree of probability to achieve the eradication of P. Aeruginosa in patients with pneumonia and to improve the prognosis for this disease. Keywords: pneumonia, Pseudomonas Aeruginosa, resistance, treatment.

scholarly journals Role of embB in natural and acquired resistance to ethambutol in mycobacteria.

1997 ◽  
Vol 41 (10) ◽  
pp. 2270-2273 ◽  
Author(s):  
F Alcaide ◽  
G E Pfyffer ◽  
A Telenti
Keyword(s):  
Nontuberculous Mycobacteria ◽  
Practical Implication ◽  
Acquired Resistance ◽  
Fold Increase ◽  
Drug Susceptibility ◽  
Natural Resistance ◽  
Intrinsic Resistance ◽  
Resistant Strains ◽  
High Level

The mycobacterial embCAB operon encodes arabinosyl transferases, putative targets of the antimycobacterial agent ethambutol (EMB). Mutations in embB lead to resistance to EMB in Mycobacterium tuberculosis. The basis for natural, intrinsic resistance to EMB in nontuberculous mycobacteria (NTM) is not known; neither is the practical implication of resistance to EMB in the absence of embB mutations in M. tuberculosis well understood. The conserved embB resistance-determining region (ERDR) of a collection of 13 strains of NTM and 12 EMB-resistant strains of M. tuberculosis was investigated. Genotypes were correlated with drug susceptibility phenotypes. High-level natural resistance to EMB (MIC, . or =64 microg/ml) was associated with a variant amino acid motif in the ERDR of M. abscessus, M. chelonae, and M. leprae. Transfer of the M. abscessus emb allele to M. smegmatis resulted in a 500-fold increase in the MICs. In M. tuberculosis, embB mutations were associated with MICs of > or =20 microg/ml while resistance not associated with an ERDR mutation generally resulted in MICs of < or =10 microg/ml. These data further support the notion that the emb region determines intrinsic and acquired resistance to EMB and might help in the reassessment of the current recommendations for the screening and treatment of infections with EMB-resistant M. tuberculosis and NTM.

scholarly journals Stepwise Upregulation of the Pseudomonas aeruginosa Chromosomal Cephalosporinase Conferring High-Level β-Lactam Resistance Involves Three AmpD Homologues

2006 ◽  
Vol 50 (5) ◽  
pp. 1780-1787 ◽  
Author(s):  
Carlos Juan ◽  
Bartolomé Moyá ◽  
José L. Pérez ◽  
Antonio Oliver
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Resistance Mechanisms ◽  
Natural Resistance ◽  
Wild Type ◽  
Triple Mutant ◽  
Major Threat ◽  
Development Of Resistance ◽  
One Step ◽  
High Level ◽  
Very High

ABSTRACT Development of resistance to the antipseudomonal penicillins and cephalosporins mediated by hyperproduction of the chromosomal cephalosporinase AmpC is a major threat to the successful treatment of Pseudomonas aeruginosa infections. Although ampD inactivation has been previously found to lead to a partially derepressed phenotype characterized by increased AmpC production but retaining further inducibility, the regulation of ampC in P. aeruginosa is far from well understood. We demonstrate that ampC expression is coordinately repressed by three AmpD homologues, including the previously described protein AmpD plus two additional proteins, designated AmpDh2 and AmpDh3. The three AmpD homologues are responsible for a stepwise ampC upregulation mechanism ultimately leading to constitutive hyperexpression of the chromosomal cephalosporinase and high-level antipseudomonal β-lactam resistance, as shown by analysis of the three single ampD mutants, the three double ampD mutants, and the triple ampD mutant. This is achieved by a three-step escalating mechanism rendering four relevant expression states: basal-level inducible expression (wild type), moderate-level hyperinducible expression with increased antipseudomonal β-lactam resistance (ampD mutant), high-level hyperinducible expression with high-level β-lactam resistance (ampD ampDh3 double mutant), and very high-level (more than 1,000-fold compared to the wild type) derepressed expression (triple mutant). Although one-step inducible-derepressed expression models are frequent in natural resistance mechanisms, this is the first characterized example in which expression of a resistance gene can be sequentially amplified through multiple steps of derepression.

scholarly journals Determinants of Intrinsic Aminoglycoside Resistance in Pseudomonas aeruginosa

2012 ◽  
Vol 56 (11) ◽  
pp. 5591-5602 ◽  
Author(s):  
Thomas Krahn ◽  
Christie Gilmour ◽  
Justin Tilak ◽  
Sebastien Fraud ◽  
Nicholas Kerr ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Cell Envelope ◽  
Acquired Resistance ◽  
Insertion Mutant ◽  
Deletion Mutants ◽  
Aminoglycoside Resistance ◽  
Content Type ◽  
Single Deletion ◽  
High Level ◽  
Increased Susceptibility

ABSTRACTScreening of a transposon insertion mutant library ofPseudomonas aeruginosafor increased susceptibility to paromomycin identified a number of genes whose disruption enhanced susceptibility of this organism to multiple aminoglycosides, including tobramycin, amikacin, and gentamicin. These included genes associated with lipid biosynthesis or metabolism (lptA,faoA), phosphate uptake (pstB), and two-component regulators (amgRS, PA2797-PA2798) and a gene of unknown function (PA0392). Deletion mutants lacking these showed enhanced panaminoglycoside susceptibility that was reversed by the cloned genes, confirming their contribution to intrinsic panaminoglycoside resistance. None of these mutants showed increased aminoglycoside permeation of the cell envelope, indicating that increased susceptibility was not related to enhanced aminoglycoside uptake owing to a reduced envelope barrier function. Several mutants (pstB,faoA, PA0392,amgR) did, however, show increased cytoplasmic membrane depolarization relative to wild type following gentamicin exposure, consistent with the membranes of these mutants being more prone to perturbation, likely by gentamicin-generated mistranslated polypeptides. Mutants lacking any two of these resistance genes in various combinations invariably showed increased aminoglycoside susceptibility relative to single-deletion mutants, confirming their independent contribution to resistance and highlighting the complexity of the intrinsic aminoglycoside resistome inP. aeruginosa. Deletion of these genes also compromised the high-level panaminoglycoside resistance of clinical isolates, emphasizing their important contribution to acquired resistance.

scholarly journals Prevalence, Risk Factors, and Molecular Epidemiology of Intestinal Carbapenem-Resistant Pseudomonas aeruginosa

2021 ◽  
Author(s):  
Yanyan Hu ◽  
Yan Qing ◽  
Jiawei Chen ◽  
Congcong Liu ◽  
Jiayue Lu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pseudomonas Aeruginosa ◽  
Gastrointestinal Tract ◽  
Resistance Genes ◽  
Acquired Resistance ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Human Gastrointestinal Tract ◽  
Content Type ◽  
Carbapenem Resistant

Pseudomonas aeruginosa may become multidrug-resistant (MDR) due to multiple inherited and acquired resistance mechanisms. The human gastrointestinal tract is known as a reservoir of P. aeruginosa and its resistance genes.

scholarly journals Metabolomics Comparison of Drug-Resistant and Drug-Susceptible Pseudomonas aeruginosa Strain (Intra- and Extracellular Analysis)

2021 ◽  
Vol 22 (19) ◽  
pp. 10820
Author(s):  
Karolina Anna Mielko ◽  
Sławomir Jan Jabłoński ◽  
Łukasz Pruss ◽  
Justyna Milczewska ◽  
Dorota Sands ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acquired Resistance ◽  
Natural Resistance ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Additional Information ◽  
Drug Resistant Bacteria ◽  
Extracellular Metabolites ◽  
Considerable Problem ◽  
Source Of Information

Pseudomonas aeruginosa is a common human pathogen belonging to the ESKAPE group. The multidrug resistance of bacteria is a considerable problem in treating patients and may lead to increased morbidity and mortality rate. The natural resistance in these organisms is caused by the production of specific enzymes and biofilm formation, while acquired resistance is multifactorial. Precise recognition of potential antibiotic resistance on different molecular levels is essential. Metabolomics tools may aid in the observation of the flux of low molecular weight compounds in biochemical pathways yielding additional information about drug-resistant bacteria. In this study, the metabolisms of two P. aeruginosa strains were compared—antibiotic susceptible vs. resistant. Analysis was performed on both intra- and extracellular metabolites. The 1H NMR method was used together with multivariate and univariate data analysis, additionally analysis of the metabolic pathways with the FELLA package was performed. The results revealed the differences in P. aeruginosa metabolism of drug-resistant and drug-susceptible strains and provided direct molecular information about P. aeruginosa response for different types of antibiotics. The most significant differences were found in the turnover of amino acids. This study can be a valuable source of information to complement research on drug resistance in P. aeruginosa.

scholarly journals Identification of RAGE and OSM as New Prognosis Biomarkers of Severe Pneumonia

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Jing Lei ◽  
Li Wang ◽  
Qian Li ◽  
Lin Gao ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Mortality Rate ◽  
Poor Prognosis ◽  
Total Bilirubin ◽  
Oxygenation Index ◽  
Severe Pneumonia ◽  
Albumin Level ◽  
Significant Decline ◽  
Survival Group ◽  
Index Level

Objective. To investigate efficiency of RAGE and OSM as new prognosis biomarkers of severe pneumonia. Methods. Eligible patients were classified into hypoxemia and nonhypoxemia groups. Meanwhile, the same cohort was divided into survival and nonsurvival groups after a post-hospital stay of 30 days. We analyzed risk factors for the hypoxia and death among these patients. Results. Compared with nonsurvival group, significant increase was noticed in PH, lymphocyte, albumin and platelet level in survival group, while significant decline was noticed in neutrophils, RBC, hemoglobin, hematocrit, creatinine, total bilirubin, CRP, PCT, OSM, RAGE and neutrophils/lymphocyte level. Oxygenation index level was related to APACHE II, LIS, SOFA, NUTRIC score, WBC, neutrophils, lymphocyte, RAGE, and albumin level ( p < 0.05 ). LIS, SOFA, NUTRIC score, lac, lymphocyte, platelet, BUN, total bilirubin, PCT, and OSM levels were associated with mortality rate ( p < 0.05 ). Conclusions. RAGE and OSM may serve as a new biomarker for poor prognosis in pneumonia patients.

Risk Factors and Outcomes Associated with Isolation of Meropenem High-Level-Resistant Pseudomonas aeruginosa

2009 ◽  
Vol 30 (8) ◽  
pp. 746-752 ◽  
Author(s):  
Kathryn J. Eagye ◽  
Joseph L. Kuti ◽  
David P. Nicolau
Keyword(s):  
Risk Factors ◽  
At Risk ◽  
Pseudomonas Aeruginosa ◽  
Foley Catheter ◽  
Antibiotic Use ◽  
Control Measures ◽  
Administrative Database ◽  
Control Group ◽  
Infection Control Measures ◽  
High Level

Objective.To determine risk factors and outcomes for patients with meropenem high–level-resistant Pseudomonas aeruginosa (MRPA) (minimum inhibitory concentration [MIC] ≥ 32 μg/mL).Design.Case-control-control.Setting.An 867-bed urban, teaching hospital.Patients.Fifty-eight MRPA case patients identified from an earlier P. aeruginosa study; 125 randomly selected control patients with meropenem-susceptible P. aeruginosa (MSPA) (MIC ≤ 4 μg/mL), and 57 control patients without P. aeruginosa (sampled by case date/location).Methods.Patient data, outcomes, and costs were obtained via administrative database. Cases were compared to each control group while controlling for time at risk (days between admission and culture, or entire length of stay [LOS] for patients without P. aeruginosa).Results.A multivariable model predicted risks for MRPA versus MSPA (odds ratio [95% confidence interval]): more admissions (in the prior 12 months) (1.41 [1.15, 1.74]), congestive heart failure (2.19 [1.03, 4.68]), and Foley catheter (2.53 [1.18, 5.45]) (adj. R2 = 0.28). For MRPA versus no P. aeruginosa, risks were age (in 5-year increments) (1.17 [1.03, 1.33]), more prior admissions (1.40 [1.08, 1.81]), and more days in the intensive care unit (1.10 [1.03, 1.18]) (adj. R2 = 0.32). Other invasive devices (including mechanical ventilation) and previous antibiotic use (including carbapenems) were nonsignificant. MRPA mortality (31%) did not differ from that of MSPA (15%) when adjusted for time at risk (P = .15) but did from mortality without P. aeruginosa (9%) (P = .01 ). Median LOS and costs were greater for MRPA patients versus MSPA patients and patients without P. aeruginosa: 30 days versus 16 and 10 (P < .01 ) and $88,425 versus $28,620 and $22,605 (P <.01).Conclusions.Although antibiotic use has been shown to promote resistance, our data found that prior antibiotic use was not associated with MRPA acquisition. However, admission frequency and Foley catheters were, suggesting that infection control measures are essential to reducing MRPA transmission.

scholarly journals Multifocal outbreaks of metallo-beta-lactamase-producing Pseudomonas aeruginosa resistant to broad-spectrum beta-lactams, including carbapenems.

1996 ◽  
Vol 40 (2) ◽  
pp. 349-353 ◽  
Author(s):  
K Senda ◽  
Y Arakawa ◽  
K Nakashima ◽  
H Ito ◽  
S Ichiyama ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Broad Spectrum ◽  
Early Recognition ◽  
Carbapenem Resistance ◽  
Hybridization Analysis ◽  
Beta Lactamase ◽  
Beta Lactams ◽  
Imipenem Resistance ◽  
High Level ◽  
Lactamase Gene

A total of 3,700 Pseudomonas aeruginosa isolates were collected from 17 general hospitals in Japan from 1992 to 1994. Of these isolates, 132 carbapenem-resistant strains were subjected to DNA hybridization analysis with the metallo-beta-lactamase gene (blaIMP)-specific probe. Fifteen strains carrying the metallo-beta-lactamase gene were identified in five hospitals in different geographical areas. Three strains of P. aeruginosa demonstrated high-level imipenem resistance (MIC, > or = 128 micrograms/ml), two strains exhibited low-level imipenem resistance (MIC, < or = 4 micrograms/ml), and the rest of the strains were in between. These results revealed that the acquisition of a metallo-beta-lactamase gene alone does not necessarily confer elevated resistance to carbapenems. In several strains, the metallo-beta-lactamase gene was carried by large plasmids, and carbapenem resistance was transferred from P. aeruginosa to Escherichia coli by electroporation in association with the acquisition of the large plasmid. Southern hybridization analysis and genomic DNA fingerprinting profiles revealed different genetic backgrounds for these 15 isolates, although considerable similarity was observed for the strains isolated from the same hospital. These findings suggest that the metallo-beta-lactamase-producing P. aeruginosa strains are not confined to a unique clonal lineage but proliferated multifocally by plasmid-mediated dissemination of the metallo-beta-lactamase gene in strains of different genetic backgrounds. Thus, further proliferation of metallo-beta-lactamase-producing strains with resistance to various beta-lactams may well be inevitable in the future, which emphasizes the need for early recognition of metallo-beta-lactamase-producing strains, rigorous infection control, and restricted clinical use of broad-spectrum beta-lactams including carbapenems.

scholarly journals Antibiotic Resistance Characteristics of Pseudomonas aeruginosa Isolated from Keratitis in Australia and India

Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 600
Author(s):  
Mahjabeen Khan ◽  
Fiona Stapleton ◽  
Stephen Summers ◽  
Scott A. Rice ◽  
Mark D. P. Willcox
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Genetic Variation ◽  
Acquired Resistance ◽  
Drug Resistant ◽  
Beta Lactams ◽  
Mmr Genes ◽  
Large Numbers ◽  
Indian Isolates ◽  
Sequence Types ◽  
Core Genes

This study investigated genomic differences in Australian and Indian Pseudomonas aeruginosa isolates from keratitis (infection of the cornea). Overall, the Indian isolates were resistant to more antibiotics, with some of those isolates being multi-drug resistant. Acquired genes were related to resistance to fluoroquinolones, aminoglycosides, beta-lactams, macrolides, sulphonamides, and tetracycline and were more frequent in Indian (96%) than in Australian (35%) isolates (p = 0.02). Indian isolates had large numbers of gene variations (median 50,006, IQR = 26,967–50,600) compared to Australian isolates (median 26,317, IQR = 25,681–33,780). There were a larger number of mutations in the mutL and uvrD genes associated with the mismatch repair (MMR) system in Indian isolates, which may result in strains losing their efficacy for DNA repair. The number of gene variations were greater in isolates carrying MMR system genes or exoU. In the phylogenetic division, the number of core genes were similar in both groups, but Indian isolates had larger numbers of pan genes (median 6518, IQR = 6040–6935). Clones related to three different sequence types—ST308, ST316, and ST491—were found among Indian isolates. Only one clone, ST233, containing two strains was present in Australian isolates. The most striking differences between Australian and Indian isolates were carriage of exoU (that encodes a cytolytic phospholipase) in Indian isolates and exoS (that encodes for GTPase activator activity) in Australian isolates, large number of acquired resistance genes, greater changes to MMR genes, and a larger pan genome as well as increased overall genetic variation in the Indian isolates.

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