Browsing by Author "Van Rijswijk, Amike"

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    The association between pathogen factors and clinical outcomes in patients with Staphylococcus aureus bacteraemia in a tertiary hospital, Cape Town
    (Elsevier on behalf of International Society for Infectious Diseases, 2019-11-29) Abdulgadera, Shima M.; Van Rijswijk, Amike; Whitelawa, Andrew; Newton-Foota, Mae
    Background: Staphylococcus aureus is a serious pathogen, able to cause life-threatening infections such as bacteraemia. The association between S. aureus microbial characteristics and clinical outcomes is under- investigated in African settings. This study aimed to determine the molecular epidemiology and virulence characteristics of S. aureus isolates from bacteraemic patients at Tygerberg Hospital, South Africa, and to investigate the associations between pathogen characteristics and clinical outcomes. Methods: This study included 199 S. aureus isolates collected from blood cultures between February 2015 and March 2017. Methicillin resistance was determined using disc diffusion and all resistant isolates were further characterized by staphylococcal cassette chromosome mec (SCCmec) typing. Genotyping was done using spa and agr typing, and agr functionality was assessed using the phenotypic d-haemolysin assay. Logistic regression models were performed to describe the associations between strain characteristics and the clinical outcomes methicillin resistance, in-hospital mortality, and length of stay (LOS). Results: Of the 199 S. aureus isolates collected, 27% were MRSA, and the overall crude in-hospital mortality rate was 29%. Seventy-three different spa types were identified, including seven new types. Agr I was the most common type, in 99 (49.7%) isolates, followed by agr II, III, and IV in 57 (28.6%), 37 (18.6%), and six (3%) isolates, respectively. Agr dysfunctionality was observed in 25 (13%) isolates, mostly belonging to spa-clonal complex (CC) 012. Methicillin resistance was significantly associated with hospital-acquired infection (odds ratio (OR) 4.77, 95% confidence interval (CI) 2.09–10.87). A significant increase in mortality was observed with increasing age (OR 7.48, 95% CI 2.82–19.8) and having a hospital-acquired infection (OR 2.26, 95% CI 1.12–4.55). S. aureus strains with a functional agr system showed an association with longer duration of stay (OR 1.66, 95% CI 0.93–2.99). Conclusions: We report the lowest MRSA prevalence at Tygerberg Hospital for the past 10 years, and agr dysfunctionality was shown to be driven by a certain genotype, spa-CC012. Despite the limited available clinical data, the study provided insights into associations between S. aureus epidemiology and agr-related virulence characteristics, and clinical outcomes.
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    The epidemiology and virulence characteristics of Staphylococcus aureus isolates from bacteraemic patients at Tygerberg Hospital, South Africa
    (Stellenbosch : Stellenbosch University, 2019-04-02) Van Rijswijk, Amike; Newton-Foot, Mae; Abdulgader, Shima; Whitelaw, Andrew; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology: Medical Microbiology.
    ENGLISH ABSTRACT: Introduction: Staphylococcus aureus is a versatile pathogen that produces multiple virulence factors which work together to establish and maintain infections. The accessory gene regulator (agr) locus is a quorum sensing two-component system which regulates at least 23 virulence factors. There are four different agr types, I-IV, and mutations within the agr locus may result in a dysfunctional agr. These can result in altered gene expression which may affect disease presentation and outcome. Data on the molecular epidemiology of S. aureus and its association with clinical outcome in South Africa is limited. This study aimed to determine the effect of epidemiology and agr-associated virulence characteristics on the clinical outcome of bacteraemic patients at Tygerberg Hospital. Methods: S. aureus isolates were collected from blood cultures from February 2015 to March 2017. Genotyping was performed using staphylococcal protein A (spa) typing and multi-locus sequence typing (MLST); and staphylococcal cassette chromosome mec (SCCmec) typing was performed on all methicillin resistant S. aureus (MRSA) isolates. Agr typing was performed by PCR and agr functionality was assessed using a phenotypic δ-haemolysin assay and matrix assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS). Associations between patient- and strain- characteristics, and the final outcomes mortality, methicillin resistance and length of stay were investigated by means of regression models. Results and discussion: Of the 199 S. aureus isolates collected, 27% were MRSA. Seventy three spa types were identified; reflecting a diverse population. MRSA isolates were more clonal than methicillin susceptible S. aureus (MSSA) isolates. A previously described novel variant SCCmec type (NV) and SCCmec type IV were most common among MRSA isolates. Agr type I was the dominant agr type, while agr type IV was least prevalent; consistent with the literature. The dominant clone in this study was an MRSA outbreak strain, t045-ST5-MRSA-NV, agr type II (spa-CC 002, CC5), which appears to be circulating in multiple hospital settings in South Africa. The most prevalent MSSA strain/clone was t318-ST1865, agr type III. Pandemic clones such as t037-ST239-MRSA-III, t032-ST22-MRSA-IV and t012-ST36-MRSA-II were also identified. A previously described association between MRSA and spa-CC 002 (CC5) was confirmed in this study; however this association may have been driven by the MRSA outbreak. Agr dysfunctionality was low at 12.6% and 6% using the phenotypic assay and MALDI-TOF MS respectively. Agr dysfunctionality was not clone specific and there was no difference in agr dysfunctionality between MRSA and MSSA isolates. A borderline association between agr dysfunction and shorter length of stay was identified, but needs further investigation. The overall mortality rate was 29% and older age was associated with increased mortality. Hospital acquired (HA) infections were also associated with a higher mortality, which could be explained by the complicated nature of these infections, leading to death. An association between HA infections and MRSA was identified, which is consistent with previous studies and not surprising considering antibiotic selective pressure is higher in hospitals. Conclusion: This study provides insights into the associations between S. aureus epidemiology and agr related virulence characteristics and clinical outcome, despite the limited clinical data available.