Department of Pathology

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Browsing Department of Pathology by browse.metadata.advisor "Abdulgader, Shima"

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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.