Persistent Isolation of Staphylococcus aureus in Mechanically-ventilated Patients: Impact of Host–Pathogen Factors on Outcome

Lacoma, Alícia; Gomes-Fernandes, Meissiner; Mesalles, Eduard; Arméstar, Fernándo; Prat, Cristina

doi:10.1016/j.arbres.2018.05.010

Cited by 3 publications

(7 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with the fact that among the 34 clinical cases, 7 presented development of respiratory complications and/or mortality related. All of them belonged to the pneumonia study group, which includes those patients with worse outcomes [9]. Adherence to fibronectin did not differ between isolates with one or two fnb genes, as previously shown [17].…”

Section: Discussionsupporting

confidence: 57%

“…Colonization and infection of the lower respiratory tract may involve distinct evolutionary pressures compared with the bloodstream or deep soft tissue. Clinically, repeated isolation of S. aureus from the lower respiratory tract did not correlate with worse outcomes compared with patients with only a single S. aureus tracheal aspirate culture [9]. As it has been previously mentioned, from a clinical perspective, in some circumstances the diagnosis of respiratory tract infections can be complex [6].…”

Section: Discussionmentioning

confidence: 73%

“…S. aureus has been reported to be particularly difficult to eradicate from the respiratory tract in some situations [8]. In a previous study, we showed persistent isolation despite antimicrobial treatment adjusted to susceptibility testing was frequent, even in cases with isolation of methicillin susceptible isolates with no impact on clinical outcome [9]. The repeated and consecutive isolation of S. aureus in the lower respiratory tract suggests that the microorganism can survive in this particular niche.…”

Section: Introductionmentioning

confidence: 67%

“…Thus, access to sequential isolates offers an opportunity to characterize pathological host adaptation in this anatomical location. In the current study, we performed an exhaustive genotypic characterization of S. aureus clinical strains sequentially isolated from patients under mechanical ventilation [9]. Previous studies of invasive S. aureus infection have demonstrated low within-host diversity in infecting populations, and changes in regulatory genes, especially the Agr locus, associated with the development of bacteremia and invasive infections [34][35][36].…”

Section: Discussionmentioning

confidence: 99%

“…The study is observational. Patients admitted to ICU over a 2 year period (2012-2013) and from whom S. aureus was isolated in at least one endotracheal aspirate (ETA) were selected as described previously [9]. All patients at inclusion were under mechanical ventilation.…”

Section: Patients and Strainsmentioning

confidence: 99%

See 4 more Smart Citations

Genotypic and Phenotypic Characterization of Staphylococcus aureus Isolates from the Respiratory Tract in Mechanically-Ventilated Patients

Lacoma

Laabei

Sánchez-Herrero

et al. 2021

Toxins

Self Cite

View full text Add to dashboard Cite

: Staphylococcus aureus is a commensal and frequent colonizer of the upper respiratory tract. When mechanical ventilation disrupts natural defenses, S. aureus is frequently isolated from the lower airways, but distinguishing between colonization and infection is difficult. The objectives of this study were (1) to investigate the bacterial genome sequence in consecutive isolates in order to identify changes related to the pathological adaptation to the lower respiratory tract and (2) to explore the relationship between specific phenotypic and genotypic features with the patient’s study group, persistence of the clinical isolate and clinical outcome. A set of 94 clinical isolates were selected and corresponded to 34 patients that were classified as having pneumonia (10), tracheobronchitis (11) and bronchial colonization (13). Clinical strains were phenotypically characterized by conventional identification and susceptibility testing methods. Isolates underwent whole genome sequencing using Illumina HiSeq4000. Genotypic characterization was performed with an in-house pipeline (BacterialTyper). Genomic variation arising within-host was determined by comparing mapped sequences and de novo assemblies. Virulence factors important in staphylococcal colonization and infection were characterized using previously established functional assays. (1) Toxin production was assessed using a THP-1 cytotoxicity assay, which reports on the gross cytotoxicity of individual isolates. In addition, we investigated the expression of the major virulence factor, alpha-toxin (Hla) by Western blot. (2) Adhesion to the important extracellular matrix molecule, fibronectin, was determined using a standardized microtitre plate assay. Finally, invasion experiments using THP-1 and A539 cell lines and selected clinical strains were also performed. Repeated isolation of S. aureus from endotracheal aspirate usually reflects persistence of the same strain. Within-host variation is detectable in this setting, but it shows no evidence of pathological adaptation related to virulence, resistance or niche adaptations. Cytotoxicity was variable among isolates with 14 strains showing no cytotoxicity, with these latter presenting an unaltered Fn binding capacity. No changes on cytotoxicity were reported when comparing study groups. Fn binding capacity was reported for almost all strains, with the exception of two strains that presented the lowest values. Strains isolated from patients with pneumonia presented a lower capacity of adhesion in comparison to those isolated during tracheobronchitis (p = 0.002). Hla was detected in 71 strains (75.5%), with most of the producer strains in pneumonia and bronchial colonization group (p = 0.06). In our cohort, Hla expression (presence or absence) in sequential isolates was usually preserved (70%) although in seven cases the expression varied over time. No relationship was found between low cytotoxicity and intracellular persistence in invasion experiments. In our study population, persistent S aureus isolation from airways in ventilated patients does not reflect pathological adaptation. There is an important diversity of sequence types. Cytotoxicity is variable among strains, but no association with study groups was found, whereas isolates from patients with pneumonia had lower adhesion capability. Favorable clinical outcome correlated with increased bacterial adhesion in vitro. Most of the strains isolated from the lower airways were Hla producers and no correlation with an adverse outcome was reported. The identification of microbial factors that contribute to virulence is relevant to optimize patient management during lower respiratory tract infections.

show abstract

Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: Patients and Strainsmentioning

confidence: 99%

See 3 more Smart Citations

Genotypic and Phenotypic Characterization of Staphylococcus aureus Isolates from the Respiratory Tract in Mechanically-Ventilated Patients

Lacoma

Laabei

Sánchez-Herrero

et al. 2021

Toxins

Self Cite

View full text Add to dashboard Cite

show abstract

Direct Quantitative Immunochemical Analysis of Autoinducer Peptide IV for Diagnosing and Stratifying Staphylococcus aureus Infections

et al. 2022

Self Cite

View full text Add to dashboard Cite

An immunochemical strategy to detect and quantify AIP-IV, the quorum sensing (QS) signaling molecule produced by Staphylococcus aureus agr type IV, is reported here for the first time. Theoretical calculations and molecular modeling studies have assisted on the design and synthesis of a suitable peptide hapten (AIPIVS), allowing to obtain high avidity and specific antibodies toward this peptide despite its low molecular weight. The ELISA developed achieves an IC 50 value of 2.80 ± 0.17 and an LOD of 0.19 ± 0.06 nM in complex media such as 1/2 Tryptic Soy Broth. Recognition of other S. aureus AIPs (I–III) is negligible (cross-reactivity below 0.001%), regardless of the structural similarities. A pilot study with a set of clinical isolates from patients with airways infection or colonization demonstrates the potential of this ELISA to perform biomedical investigations related to the role of QS in pathogenesis and the association between dysfunctional agr or the agr type with unfavorable clinical outcomes. The AIP-IV levels could be quantified in the low nanomolar range in less than 1 h after inoculating agr IV-genotyped isolates in the culture broth, while those genotyped as I–III did not show any immunoreactivity after a 48 h growth, pointing to the possibility to use this technology for phenotyping S. aureus . The research strategy here reported can be extended to the rest of the AIP types of S. aureus , allowing the development of powerful multiplexed chips or point-of-care (PoC) diagnostic devices to unequivocally identify its presence and its agr type on samples from infected patients.

show abstract

Novel Intracellular Antibiotic Delivery System Against Staphylococcus Aureus : Cloxacillin-Loaded Poly( D , L -Lactide-Co-Glycolide) Acid Nanoparticles

Lacoma

Usón

Mendoza

et al. 2020

Nanomedicine (Lond.)

Self Cite

View full text Add to dashboard Cite

Aim: First, to compare in vitro minimum inhibitory concentrations (MIC) of free cloxacillin and cloxacillin-containing nanoparticles (NP) against methicillin-susceptible (MSSA) and resistant Staphylococcus aureus (MRSA) and second, to assess NP antimicrobial activity against intracellular S. aureus. Methods: Poly(d,l-lactide-co-glycolide) acid (PLGA)-NP were loaded with cloxacillin and physico-chemically characterized. MICs were determined for reference strains Newman-(MSSA) and USA300-(MRSA). Murine alveolar macrophages were infected, and bacterial intracellular survival was assessed after incubating with free-cloxacillin or PLGA-cloxacillin-NP. Results & conclusion: For both isolates, MICs for antibiotic-loaded-NP were lower than those obtained with free cloxacillin, indicating that the drug encapsulation improves antimicrobial activity. A sustained antibiotic release was demonstrated when using the PLGA-cloxacillin-NP. When considering the lowest concentrations, the use of drug-loaded NP enabled a higher reduction of intracellular bacterial load.

show abstract

Persistent Isolation of Staphylococcus aureus in Mechanically-ventilated Patients: Impact of Host–Pathogen Factors on Outcome

Cited by 3 publications

References 12 publications

Genotypic and Phenotypic Characterization of Staphylococcus aureus Isolates from the Respiratory Tract in Mechanically-Ventilated Patients

Genotypic and Phenotypic Characterization of Staphylococcus aureus Isolates from the Respiratory Tract in Mechanically-Ventilated Patients

Direct Quantitative Immunochemical Analysis of Autoinducer Peptide IV for Diagnosing and Stratifying Staphylococcus aureus Infections

Novel Intracellular Antibiotic Delivery System Against Staphylococcus Aureus : Cloxacillin-Loaded Poly( D , L -Lactide-Co-Glycolide) Acid Nanoparticles

Contact Info

Product

Resources

About