Complete Genome Sequence of Pseudomonas aeruginosa CMC-097, Isolated from a Ventilator-Associated Pneumonia Patient, Containing a Novel Carbapenem Resistance Class 1 Integron.
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SUBMITTER: Rao J
PROVIDER: S-EPMC8411920 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Ventilator-associated pneumonia is the most common infection in intensive care unit patients associated with high morbidity rates and elevated economic costs; Pseudomonas aeruginosa is one of the most frequent bacteria linked with this entity, with a high attributable mortality despite adequate treatment that is increased in the presence of multiresistant strains, a situation that is becoming more common in intensive care units. In this manuscript, we review the current management of ventilator-associated pneumonia due to P. aeruginosa, the most recent antipseudomonal agents, and new adjunctive therapies that are shifting the way we treat these infections. We support early initiation of broad-spectrum antipseudomonal antibiotics in present, followed by culture-guided monotherapy de-escalation when susceptibilities are available. Future management should be directed at blocking virulence; the role of alternative strategies such as new antibiotics, nebulized treatments, and vaccines is promising.
| S-EPMC4725638 | biostudies-other
Project description:We report the complete genome of clinical strain Pseudomonas aeruginosa CMC-115, which was isolated from an acute ventilator-associated pneumonia patient. Illumina sequencing reads were assembled using Geneious to yield a 6,375,262-bp circular chromosome that exhibited an unusual ferrichrome receptor in the pyoverdine synthesis locus and the absence of type 3 secretion system genes.
| S-EPMC7378034 | biostudies-literature
Project description:Four bla(VIM-2) gene-harboring Pseudomonas aeruginosa strains were identified. These strains possessed a class 1 integron harboring ORF1, bla(VIM-2), and aacA4 gene cassettes. The transposon-mediated horizontal spread of the bla(VIM-2) gene among these strains was suggested, which increases the threat that the bla(VIM-2) gene will disseminate among diverse genera of bacteria.
| S-EPMC321541 | biostudies-literature
Project description:RationalePseudomonas aeruginosa is one of the leading causes of gram-negative ventilator-associated pneumonia (VAP) associated with a mortality rate of 34 to 68%. Recent evidence suggests that P. aeruginosa in patients with VAP may persist in the alveolar space despite adequate antimicrobial therapy. We hypothesized that failure to eradicate P. aeruginosa from the lung is linked to type III secretory system (TTSS) isolates.ObjectivesTo determine the mechanism by which infection with P. aeruginosa in patients with VAP may evade the host immune response.MethodsThirty-four patients with P. aeruginosa VAP underwent noninvasive bronchoalveolar lavage (BAL) at the onset of VAP and on Day 8 after initiation of antibiotic therapy. Isolated pathogens were analyzed for secretion of type III cytotoxins. Neutrophil apoptosis in BAL fluid was quantified by assessment of nuclear morphology on Giemsa-stained cytocentrifuge preparations. Neutrophil elastase was assessed by immunoenzymatic assay.Measurements and main resultsTwenty-five out of the 34 patients with VAP secreted at least one of type III proteins. There was a significant difference in apoptotic rate of neutrophils at VAP onset between those strains that secreted cytotoxins and those that did not. Neutrophil elastase levels were positively correlated with the rate of apoptosis (r = 0.43, P < 0.01). Despite adequate antimicrobial therapy, 13 out of 25 TTSS(+) isolates were recovered at Day 8 post-VAP, whereas eradication was achieved in all patients who had undetectable levels of type III secretion proteins.ConclusionsThe increased apoptosis in neutrophils by the TTSS(+) isolates may explain the delay in eradication of Pseudomonas strains in patients with VAP. Short-course antimicrobial therapy may not be adequate in clearing the infection with a TTSS secretory phenotype.
| S-EPMC2542430 | biostudies-literature
Project description:BackgroundThe objective of this study was to evaluate the virulence of P. aeruginosa ventilator-associated pneumonia (VAP) strains (cases) in terms of biofilm production and other phenotypic and genotypic virulence factors compared to P. aeruginosa strains isolated from other infections (controls).MethodsBiofilm production was tested to assess biomass production and metabolic activity using crystal violet binding assay and XTT assay, respectively. Pigment production (pyocyanin and pyoverdine) was evaluated using cetrimide agar. Virulence genes were detected by conventional multiplex PCR and virulence was tested in an in vivo model in Galleria mellonella larvae.ResultsWe did not find statistically significant differences between VAP and no-VAP strains (p >?0.05) regarding biofilm production. VAP strains had no production of pyocyanin after 24?h of incubation (p =?0.023). The distribution of virulence genes between both groups were similar (p?>?0.05). VAP strains were less virulent than non-VAP strains in an in vivo model of G. mellonella (p <?0.001).ConclusionThe virulence of VAP-Pseudomonas aeruginosa does not depend on biofilm formation, production of pyoverdine or the presence of some virulence genes compared to P. aeruginosa isolated from non-invasive locations. However, VAP strains showed attenuated virulence compared to non-VAP strains in an in vivo model of G. mellonella.
| S-EPMC7706020 | biostudies-literature
Project description:Bacterial gene islands add to the genetic repertoire of opportunistic pathogens. Here, we perform comparative analyses of three Pseudomonas aeruginosa strains isolated sequentially over a 3-week period from a patient with ventilator-associated pneumonia (VAP) who received clindamycin and piperacillin-tazobactam as part of their treatment regime. While all three strains appeared to be clonal by standard pulsed-field gel electrophoresis, whole-genome sequencing revealed subtle alterations in the chromosomal organization of the last two strains; specifically, an inversion event within a novel 124-kb gene island (PAGI 12) composed of 137 open reading frames [ORFs]. Predicted ORFs in the island included metabolism and virulence genes. Overexpression of a gene island-borne putative β-lactamase gene was observed following piperacillin-tazobactam exposure and only in those strains that had undergone the inversion event, indicating altered gene regulation following genomic remodeling. Examination of a separate cohort of 76 patients with VAP for integration at this tRNA(lys) recombination site demonstrated that patients exhibiting evidence of integration at this site had significantly higher 28-day mortality. These findings provide evidence that P. aeruginosa can integrate, rapidly remodel, and express exogenous genes, which likely contributes to its fitness in a clinical setting.
| S-EPMC4097748 | biostudies-literature
Project description:During a ?-lactam resistance surveillance study, 12 IMP-18-positive Pseudomonas aeruginosa isolates belonging to 9 different pulsed-field gel electrophoresis groups were identified. In nine isolates, a class I integron with a novel gene array was identified that contained bla(IMP-18) and bla(OXA-224), while in two isolates the class I integron contained bla(IMP-18) and bla(OXA-2) but in a new arrangement. Our findings show the dissemination of two novel class I integrons in P. aeruginosa from different regions of Puerto Rico.
| S-EPMC3318352 | biostudies-literature
Project description:Only limited data exist on Pseudomonas aeruginosa ventilator-associated pneumonia (VAP) treated with imipenem, meropenem, or doripenem. Therefore, we conducted a prospective observational study in 169 patients who developed Pseudomonas aeruginosa VAP. Imipenem, meropenem, and doripenem MICs for Pseudomonas aeruginosa isolates were determined using Etests and compared according to the carbapenem received. Among the 169 isolates responsible for the first VAP episode, doripenem MICs were lower (P<0.0001) than those of imipenem and meropenem (MIC50s, 0.25, 2, and 0.38, respectively); 61%, 64%, and 70% were susceptible to imipenem, meropenem, and doripenem, respectively (P was not statistically significant). Factors independently associated with carbapenem resistance were previous carbapenem use (within 15 days) and mechanical ventilation duration before VAP onset. Fifty-six (33%) patients had at least one VAP recurrence, and 56 (33%) died. Factors independently associated with an unfavorable outcome (recurrence or death) were a high day 7 sequential organ failure assessment score and mechanical ventilation dependency on day 7. Physicians freely prescribed a carbapenem to 88 patients: imipenem for 32, meropenem for 24, and doripenem for 32. The remaining 81 patients were treated with various antibiotics. Imipenem-, meropenem-, and doripenem-treated patients had similar VAP recurrence rates (41%, 25%, and 22%, respectively; P=0.15) and mortality rates (47%, 25%, and 22%, respectively; P=0.07). Carbapenem resistance emerged similarly among patients treated with any carbapenem. No carbapenem was superior to another for preventing carbapenem resistance emergence.
| S-EPMC3957866 | biostudies-other
Project description:BACKGROUND:Probiotics could prevent Pseudomonas aeruginosa colonization in lower respiratory tract (LRT) and reduced P. aeruginosa ventilator-associated pneumonia (VAP) rate. Recent studies also suggested that probiotics could improve lung inflammation in mice infected with P. aeruginosa. It seems that microbiota regulation may be a potential therapy for P. aeruginosa VAP patients. However, we know less about the LRT microbial composition and its correlation with prognosis in P. aeruginosa VAP patients. This study aimed to characterize LRT microbiota in P. aeruginosa VAP patients and explore the relationship between microbiota and patient prognosis. METHODS:Deep endotracheal secretions were sampled from subjects via intubation. Communities were identified by 16S ribosomal RNA gene sequencing. The relationship between microbiota and the prognosis of P. aeruginosa VAP patients were evaluated. Clinical pulmonary infection score and the survival of intensive care unit were both the indicators of patient prognosis. RESULTS:In this study, the LRT microbial composition of P. aeruginosa VAP patients was significantly different from non-infected intubation patients, and showed significant individual differences, forming two clusters. According to the predominant phylum of each cluster, these two clusters were named Pro cluster and Fir-Bac cluster respectively. Patients from Pro cluster were dominated by Proteobacteria (adj.P?<?0.001), while those from Fir-Bac cluster were dominated by Firmicutes, and Bacteroidetes (both adj.P?<?0.001). These two varied clusters (Pro and Fir-Bac cluster) were associated with the patients' primary disease (?2-test, P <?0.0001). The primary disease of the Pro cluster mainly included gastrointestinal disease (63%), and the Fir-Bac cluster was predominantly respiratory disease (89%). During the two-week dynamic observation period, despite the use of antibiotics, the dominant genera and Shannon diversity of the LRT microbiota did not change significantly in patients with P. aeruginosa VAP. In prognostic analysis, we found a significant negative correlation between Lactobacillus and clinical pulmonary infection score on the day of diagnosis (P?=?0.014); but we found no significant difference of microbial composition between survivors and non-survivors. CONCLUSIONS:LRT microbial composition was diversified among P. aeruginosa VAP patients, forming two clusters which were associated with the primary diseases of the patients.
| S-EPMC6062970 | biostudies-literature
Project description:IntroductionVentilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa is a major cause of morbidity and mortality in hospital intensive care units (ICU). Rapid identification of P. aeruginosa-derived markers in easily accessible patients' samples can enable an early detection of P. aeruginosa VAP (VAP-PA), thereby stewarding antibiotic use and improving clinical outcomes.MethodsMetabolites were analysed using liquid chromatography-mass spectrometry (LC-MS) in prospectively collected urine samples from mechanically ventilated patients admitted to the Antwerp University Hospital ICU. Patients were followed from the start of mechanical ventilation (n = 100 patients) till the time of clinical diagnosis of VAP (n = 13). Patients (n = 8) in whom diagnosis of VAP was further confirmed by culturing respiratory samples and urine samples were studied for semi-quantitative metabolomics.ResultsWe first show that multivariate analyses highly discriminated VAP-PA from VAP-non-PA as well as from the pre-infection groups (R 2 = .97 and .98, respectively). A further univariate analysis identified 58 metabolites that were significantly elevated or uniquely present in VAP-PA compared to the VAP-non-PA and pre-infection groups (P < .05). These comprised both a known metabolite of histidine as well as a novel nicotine metabolite. Most interestingly, we identified 3 metabolites that were not only highly upregulated for, but were also highly specific to, VAP-PA, as these metabolites were completely absent in all pre-infection timepoints and in VAP-non-PA group.ConclusionsConsiderable differences exist between urine metabolites in VAP-PA compared to VAP due to other bacterial aetiologies as well to non-VAP (pre-infection) timepoints. The unique urinary metabolic biomarkers we describe here, if further validated, could serve as highly specific diagnostic biomarkers of VAP-PA.
| S-EPMC9112676 | biostudies-literature