Complete Genome Sequences of Four Extensively Drug-Resistant Pseudomonas aeruginosa Strains, Isolated from Adults with Ventilator-Associated Pneumonia at a Tertiary Referral Hospital in Mexico City.
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ABSTRACT:
SUBMITTER: Espinosa-Camacho LF
PROVIDER: S-EPMC5589533 | biostudies-literature | 2017 Sep
REPOSITORIES: biostudies-literature
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Complete Genome Sequences of Four Extensively Drug-Resistant <i>Pseudomonas aeruginosa</i> Strains, Isolated from Adults with Ventilator-Associated Pneumonia at a Tertiary Referral Hospital in Mexico City.
Espinosa-Camacho Luis F LF Delgado Gabriela G Soberón-Chávez Gloria G Alcaraz Luis D LD Castañon Jorge J Morales-Espinosa Rosario R
Genome announcements 20170907 36
Four extensively drug-resistant <i>Pseudomonas aeruginosa</i> strains, isolated from patients with pneumonia, were sequenced using PacBio RS-II single-molecule real-time (SMRT) technology. Genome sequence analysis identified great variability among mobile genetic elements, as well as some previously undescribed genomic islands and new variants of class 1 integrons (In1402, In1403, In1404, and In1408). ...[more]
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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.
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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.
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Project description:Background This study describes the disease burden, clinical characteristics, antibiotic management, impact of multidrug resistance and outcome of Pseudomonas aeruginosa bloodstream infection (PABSI) among children admitted to a tertiary referral hospital for children in Cape Town, South Africa. Methods A retrospective descriptive study was conducted at a paediatric referral hospital in Cape Town, South Africa. Demographic and clinical details, antibiotic management and patient outcome information were extracted from medical and laboratory records. Antibiotic susceptibility results of identified organisms were obtained from the National Health Laboratory Service database. Results The incidence risk of PABSI was 5.4 (95% CI: 4.34–6.54) PABSI episodes / 10,000 hospital admissions and the most common presenting feature was respiratory distress, 34/91 (37.4%). Overall, 69/91 (75.8%) of the PA isolates were susceptible to all antipseudomonal antibiotic classes evaluated. Fifty (54.9%) of the PABSI episodes were treated with appropriate empiric antibiotic therapy. The mortality rate was 24.2% and in multivariable analysis, empiric antibiotic therapy to which PA isolates were not susceptible, infections present on admission, and not being in the intensive care unit at the time that PABSI was diagnosed were significantly associated with 14-day mortality. Conclusions PABSI caused appreciable mortality, however, appropriate empiric antibiotic therapy was associated with reduced 14-day mortality.
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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.
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