Impact of Staphylococcus aureus phenotype and genotype on the clinical characteristics and outcome of infective endocarditis. A multicentre, longitudinal, prospective, observational study

Fernández-Hidalgo, Núria; Ribera, Aída; Larrosa, Nieves; Viedma, Ester; Origüen, Julia; Alarcón, Arı́stides de; Fariñas, María Carmen; Sáez, Carmen; Peña, Carmen; Múñez, Elena; López, Ma Victoria García; Gavaldá, Joan; Pérez-Montarelo, Dafne; Cháves, Fernando; Almirante, Benito

doi:10.1016/j.cmi.2017.12.002

Cited by 43 publications

(22 citation statements)

References 38 publications

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“…After initial studies described worse outcomes for methicillin-resistant strains with high vancomycin MIC values [9,30], various metaanalyses on the relevance of MIC in SA infections have associated values ≥2 μg/mL with higher mortality (OR 1.72; 95% CI: 1.34-2.21) and values ≥1.5 μg/mL with [31] and even in IE [32] and bacteremia due to MSSA with MIC ≥1.5 μg/ mL, which was associated with a higher risk of complicated bacteremia [33,34]. In contrast, a longitudinal, prospective, multicenter study of MRSA endocarditis found no association of vancomycin MIC ≥1.5 μg/mL with higher mortality, although it was related to a greater persistence of bacteremia and a higher frequency of sepsis/septic shock, peripheral embolism, and arthritis/osteomyelitis [35]. Likewise, a study on beta-lactamtreated left-sided MSSA endocarditis found no relationship between vancomycin MIC and mortality or microorganism virulence [36].…”

Section: Discussionmentioning

confidence: 85%

“…Active neoplasm, sepsis/shock, and decade of endocarditis onset (1985-1999 or 2000-2009 vs. 2010-2017) emerged as poor prognostic factors, but early surgery (within first 2 weeks) did not appear to influence the prognosis. A recent multicenter, longitudinal, observational study of SA IE (n = 213 cases) reported a mortality rate of 37% and identified a high Charlson index, congestive heart failure, CNS involvement, and sepsis/septic shock as risk factors [35].…”

Section: Discussionmentioning

confidence: 99%

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Clinical and prognostic differences between methicillin-resistant and methicillin-susceptible Staphylococcus aureus infective endocarditis

et al. 2020

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Background: S. aureus (SA) infective endocarditis (IE) has a very high mortality, attributed to the age and comorbidities of patients, inadequate or delayed antibiotic treatment, and methicillin resistance, among other causes. The main study objective was to analyze epidemiological and clinical differences between IE by methicillinresistant versus methicillin-susceptible SA (MRSA vs. MSSA) and to examine prognostic factors for SA endocarditis, including methicillin resistance and vancomycin minimum inhibitory concentration (MIC) values > 1 μg/mL to MRSA. Methods: Patients with SA endocarditis were consecutively and prospectively recruited from the Andalusia endocarditis cohort between 1984 and January 2017. Results: We studied 437 patients with SA endocarditis, which was MRSA in 13.5% of cases. A greater likelihood of history of COPD (OR 3.19; 95% CI 1.41-7.23), invasive procedures, or recognized infection focus in the 3 months before IE onset (OR 2.9; 95% CI 1.14-7.65) and of diagnostic delay (OR 3.94; 95% CI 1.64-9.5) was observed in patients with MRSA versus MSSA endocarditis. The one-year mortality rate due to SA endocarditis was 44.3% and associated with decade of endocarditis onset (1985)(1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999) (OR 8.391; 95% CI (2.82-24.9);2000-2009; 95% CI 2.92-14.06); active neoplasm (OR 6.63; 95% CI 1.7-25.5) and sepsis (OR 2.28; 95% CI 1.053-4.9). Methicillin resistance was not associated with higher IE-related mortality (49.7 vs. 43.1%; p = 0.32). Conclusion: MRSA IE is associated with COPD, previous invasive procedure or recognized infection focus, and nosocomial or healthcare-related origin. Methicillin resistance does not appear to be a decisive prognostic factor for SA IE.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Clinical and prognostic differences between methicillin-resistant and methicillin-susceptible Staphylococcus aureus infective endocarditis

et al. 2020

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“…To date, many studies have analysed the association between agr dysfunction and poor clinical outcomes of invasive S. aureus infection in various clinical settings 30,32,43,44,49,50 . Since Schweizer et al reported that SAB with dysfunctional agr was associated with excessive mortality among severely ill patients 29 , subsequent studies have demonstrated that agr dysfunction was associated with higher mortality 31,32 , and the persistence of bacteraemia www.nature.com/scientificreports/ in patients with SAB, especially in MRSA bacteraemia 7,30 .…”

Section: Discussionmentioning

confidence: 99%

Dysfunctional accessory gene regulator (agr) as a prognostic factor in invasive Staphylococcus aureus infection: a systematic review and meta-analysis

Lee

et al. 2020

Sci Rep

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The accessory gene regulator (agr) locus of Staphylococcus aureus is a quorum-sensing virulence regulator. Although there are many studies concerning the effect of dysfunctional agr on the outcomes of S. aureus infection, there is no systematic review to date. We systematically searched for clinical studies reporting outcomes of invasive S. aureus infections and the proportion of dysfunctional agr among their causative strains, and we performed a meta-analysis to obtain estimates of the odds of outcomes of invasive S. aureus infection with dysfunctional versus functional agr. Of 289 articles identified by our research strategy, 20 studies were meta-analysed for crude analysis of the impact of dysfunctional agr on outcomes of invasive S. aureus infection. Dysfunctional agr was generally associated with unfavourable outcomes (OR 1.32, 95% CI 1.05–1.66), and the impact of dysfunctional agr on outcome was more prominent in invasive methicillin-resistant S. aureus (MRSA) infections (OR 1.54, CI 1.20–1.97). Nine studies were meta-analysed for the impact of dysfunctional agr on the 30-day mortality of invasive S. aureus infection. Invasive MRSA infection with dysfunctional agr exhibited higher 30-day mortality (OR 1.40, CI 1.03–1.90) than that with functional agr. On the other hand, invasive MSSA infection with dysfunctional agr exhibited lower 30-day mortality (OR 0.51, CI 0.27–0.95). In the post hoc subgroup analysis by the site of MRSA infection, dysfunctional agr was associated with higher 30-day mortality in MRSA pneumonia (OR 2.48, CI 1.17–5.25). The effect of dysfunctional agr on the outcome of invasive S. aureus infection may vary depending on various conditions, such as oxacillin susceptibility and the site of infection. Dysfunctional agr was generally associated with unfavourable clinical outcomes and its effect was prominent in MRSA and pneumonia. Dysfunctional agr may be applicable for outcome prediction in cases of invasive MRSA infection with hardly eradicable foci such as pneumonia.

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“…These strains were obtained from different sources in hospitals geographically distant from each other spread across the territory of Spain (Table 1 ). Specifically, these strains were identified in 10 different collections: six were single-center studies developed at the Hospital 12 de Octubre in Madrid, and the remaining four corresponded to multi-center studies developed at various Spanish hospitals (Muñoz-Gallego et al, 2017 ; San-Juan et al, 2017 ; Fernández-Hidalgo et al, 2018 ). The main focus and objective of the studies for which these strains were collected was source of staphylococcal bacteremia, mainly endocarditis ( N = 214), catheter-related bacteremia (CRB) ( N = 212), skin and soft tissue infections (SSTI) ( N = 66), and bone and joint infections ( N = 100).…”

Section: Methodsmentioning

confidence: 99%

Molecular Epidemiology of Staphylococcus aureus Bacteremia: Association of Molecular Factors With the Source of Infection

et al. 2018

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Staphylococcus aureus bacteremia (SAB) is associated with high morbidity and mortality, which varies depending on the source of infection. Nevertheless, the global molecular epidemiology of SAB and its possible association with specific virulence factors remains unclear. Using DNA microarrays, a total of 833 S. aureus strains (785 SAB and 48 colonizing strains) collected in Spain over a period of 15 years (2002–2017) were characterized to determine clonal complex (CC), agr type and repertoire of resistance and virulence genes in order to provide an epidemiological overview of CCs causing bloodstream infection, and to analyze possible associations between virulence genes and the most common sources of bacteremia. The results were also analyzed by acquisition (healthcare-associated [HA] and community-acquired [CA]), methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) strains, and patient age (adults vs. children). Our results revealed high clonal diversity among SAB strains with up to 28 different CCs. The most prevalent CCs were CC5 (30.8%), CC30 (20.3%), CC45 (8.3%), CC8 (8.4%), CC15 (7.5%), and CC22 (5.9%), which together accounted for 80% of all cases. A higher proportion of CC5 was found among HA strains than CA strains (35.6 vs. 20.2%, p < 0.001). CC5 was associated with methicillin resistance (14.7 vs. 79.4%, p < 0.001), whereas CC30, CC45, and CC15 were correlated with MSSA strains (p < 0.001). Pathogen-related molecular markers significantly associated with a specific source of bacteremia included the presence of sea, undisrupted hlb and isaB genes with catheter-related bacteremia; sed, splE, and fib genes with endocarditis; undisrupted hlb with skin and soft tissue infections; and finally, CC5, msrA resistance gene and hla gene with osteoarticular source. Our study suggests an association between S. aureus genotype and place of acquisition, methicillin resistance and sources of bloodstream infection, and provides a valuable starting point for further research insights into intrinsic pathogenic mechanisms involved in the development of SAB.

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Impact of Staphylococcus aureus phenotype and genotype on the clinical characteristics and outcome of infective endocarditis. A multicentre, longitudinal, prospective, observational study

Cited by 43 publications

References 38 publications

Clinical and prognostic differences between methicillin-resistant and methicillin-susceptible Staphylococcus aureus infective endocarditis

Clinical and prognostic differences between methicillin-resistant and methicillin-susceptible Staphylococcus aureus infective endocarditis

Dysfunctional accessory gene regulator (agr) as a prognostic factor in invasive Staphylococcus aureus infection: a systematic review and meta-analysis

Molecular Epidemiology of Staphylococcus aureus Bacteremia: Association of Molecular Factors With the Source of Infection

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