Evaluation of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia: Epidemiology, clinical characteristics, and outcomes in the older patients in a tertiary teaching hospital in Malaysia.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a major concern in the global healthcare system. However, data from Asian regions dealing with the singularity of this infection in older persons is lacking. We aimed to identify the differences in the clinical characteristics and outcomes of MRSA bacteremia between adults aged 18-64 and ≥ 65 years. METHODS: A retrospective study cohort was conducted at the University Malaya Medical Centre (UMMC) on cases of MRSA bacteremia from 2012 to 2016. Patient demographic and clinical data were collected for risk factors analyses. RESULTS: New cases of MRSA bacteremia showed a trend of increase from 0.12 to 100 admissions in 2012 to 0.17 per 100 admissions in 2016 but a drop was observed in 2014 (0.07 per 100 admissions). Out of the 275 patients with MRSA bacteremia, 139 (50.5%) patients were aged ≥ 65 years old. Co-morbidities and severity at presentation were significantly higher among older adults, including diabetes mellitus (p = 0.035), hypertension (p = 0.001), and ischemic heart disease (p < 0.001), as well as higher Charlson Comorbidity Index (p < 0.001) and Pitt bacteremia scores (p = 0.016). Central line-associated bloodstream infections were more common among younger patients (37.5% vs. 17.3% in older patients, p < 0.001), while skin and soft tissue infections are more frequent among older adults (20.9% vs. 10.3% in younger patients, p = 0.016). All-cause mortality and in-hospital mortality were significantly higher in older patients (82.7% and 56.1% vs. 63.2% and 28.7% in younger patients, p < 0.001). Multivariate analysis revealed age ≥ 65 years (adjusted odds ratio: 3.36; 95% confidence interval: 1.24-9.13), Pitt score ≥ 3 (2.15; 1.54-3.01), hospital (6.12; 1.81-20.72) and healthcare (3.19; 1.30-7.81) acquisition of MRSA, indwelling urinary catheters (5.43; 1.39-21.23), inappropriate targeted treatment (8.08; 1.15-56.86), lack of infectious disease team consultation (2.90; 1.04-8.11) and hypoalbuminemia (3.31; 1.25-8.79), were significant risk factors for 30-day mortality. CONCLUSION: Older patients' risk of mortality from MRSA bacteremia was three times higher than younger patients. Our data will contribute to developing and validating a robust scoring system for risk-stratifying patients to achieve better management and improved clinical outcomes.

Investigation of biofilm formation in methicillin-resistant Staphylococcus aureus associated with bacteraemia in a tertiary hospital.

Biofilm formation is an important physiological process in Staphylococcus aureus (S. aureus) that can cause infections in humans. In this study, the ability of 36 methicillin-resistant S. aureus (MRSA) clinical isolates to form biofilm was studied based on genotypic and phenotypic approaches. These isolates were genotyped based on the microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) and biofilm-associated genes (icaAD) via polymerase chain reactions. Phenotyping was performed based on the determination of the strength of biofilm formation of MRSA isolates in vitro. The most prevalent MSCRAMMs and biofilm-associated genes were clfA, eno, and icaD, followed by clfB. The fnbB (38.9%) and ebpS (11.1%) occurred less frequently among the MRSA isolates, while bbp and fnbA genes were absent from all isolates. The MRSA isolates were mostly moderate to strong biofilm formers, despite the heterogeneity of the MSCRAMM profiles. MRSA isolates from different infection sources (primary, catheter-related bloodstream, or secondary infections) were capable of forming strong biofilms. However, persistent bacteraemia was observed only in 19.4% of the MRSA-infected individuals. This study suggested that persistent MRSA bacteraemia in patients might not be associated with the biofilm-forming ability of the isolates.

Genomic analysis revealed a novel genotype of methicillin-susceptible Staphylococcus aureus isolated from a fatal sepsis case in dengue patient.

Staphylococcus aureus (S. aureus) is an opportunistic pathogen capable of causing serious health implications in susceptible individuals once it invades the host's protective barriers. Methicillin-susceptible S. aureus (MSSA) often receives lesser attention although it has been frequently associated with serious infections in human. We aim to investigate the genomic features of a highly virulent yet pan susceptible MSSA strain (coded as HS-MSSA) which caused concurrent bacteraemia in a dengue patient, ultimately resulted in sepsis death of the patient. Whole genome sequence analysis was performed. The draft genome of HS-MSSA is approximately 2.78 Mb (GC content = 32.7%) comprising of 2637 predicted coding sequences. In silico genotyping of the HS-MSSA strain revealed a novel combined genotype (t091/ST2990). The HS-MSSA carries a SaPIn1-like pathogenicity island that harbours the staphylococcal enterotoxin and enterotoxin-like genes (sec3 and selL). The strain-specific ß-lactamase (blaZ)-bearing plasmid region was identified in HS-MSSA. Core genome phylogeny showed that the HS-MSSA strain shared a common ancestry with the European MRSA clone. We report herein the genomic features of an MSSA lineage with novel genotype previously not reported elsewhere.

Methicillin-resistant Staphylococcus aureus bacteraemia, 2003-2015: Comparative evaluation of changing trends in molecular epidemiology and clinical outcomes of infections.

Methicillin-resistant Staphylococcus aureus (MRSA) is a prominent pathogen causing invasive infections such as bacteraemia. The continued excessive use of antibiotics to treat MRSA infections has resulted in the evolution of antimicrobial resistant of S. aureus. This study aims to perform a comparative evaluation of changing trends in molecular epidemiology of MRSA and clinical characteristics of patients. This study shows that ST22-MRSA-IV has gradually replaced ST239-MRSA-III as the predominant MRSA clone in the tertiary teaching hospital studied. Independent predictors of mortality among patients included devices in situ at the time of infection, pre-exposure to macrolides, catheter-related bloodstream infection and mono-microbial infection. Hence, our study affirmed community-associated MRSA, which was previously identified from individuals without any exposure to healthcare settings, has now emerged in healthcare settings, causing healthcare-associated MRSA infections.

Atypical Presentation of Methicillin-Susceptible Staphylococcus aureus Infection in a Dengue-Positive Patient: A Case Report with Virulence Genes Analysis.

Concurrent bacteraemia in patients with dengue fever is rarely reported. We report a case of a patient who initially presented with symptoms typical of dengue fever but later succumbed to septic shock caused by hypervirulent methicillin-susceptible Staphylococcus aureus (MSSA). A 50-year-old female patient with hypertension and diabetes mellitus presented with typical symptoms of dengue fever. Upon investigation, the patient reported having prolonged fever for four days prior to hospitalization. Within 24 hours post-admission, the patient developed pneumonia and refractory shock, and ultimately succumbed to multiple-organs failure. Microbiological examination of the blood culture retrieved a pan susceptible MSSA strain. Genomic sequence analyses of the MSSA strain identified genes encoding staphylococcal superantigens (enterotoxin staphylococcal enterotoxin C 3 (SEC3) and enterotoxin-like staphylococcal enterotoxins-like toxin L (SElL)) that have been associated with toxic shock syndrome in human hosts. Genes encoding important toxins (Panton-Valentine leukocidins, alpha-haemolysin, protein A) involved in the development of staphylococcal pneumonia were also present in the MSSA genome. Staphylococcus aureus co-infections in dengue are uncommon but could be exceptionally fatal if caused by a toxin-producing strain. Clinicians should be aware of the risks and signs of sepsis in dengue fever, thus allowing early diagnosis and starting of antibiotic treatment in time to lower the mortality and morbidity rates.

Predominance of ST22-MRSA-IV Clone and Emergence of Clones for Methicillin-Resistant Staphylococcus aureus Clinical Isolates Collected from a Tertiary Teaching Hospital Over a Two-Year Period.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common nosocomial pathogens, causing mild to severe infections. This study aimed to determine the genotypic and phenotypic characteristics of clinical MRSA isolates collected from a teaching hospital from 2014 - 2015. These isolates were genotyped by multilocus sequence typing, staphylococcal cassette chromosomal mec (SCCmec) typing, virulence genes detection, and pulsed-field gel electrophoresis; they were phenotyped based on their antibiotics susceptibility profiles. The most prevalent sequence type was ST22. ST3547 was identified from a blood isolate from 2015. Three SCCmec types (III in 26.26%, IV in 70.71%, and V in 3.03% isolates) were detected. Agr type I, II, and III were also detected among the isolates. The most prevalent virulence genes found were hemolysin (100%) and intracellular adhesion (91.9%). At least one staphylococcal enterotoxin was detected in 83 (83.8%) isolates. All the isolates were susceptible to vancomycin (minimum inhibitory concentration ≤ 2 µg/mL). Statistical analysis revealed a significant increase in hypertension (p = 0.035), dyslipidemia and obesity (p = 0.046), and previous exposure to any quinolone (p = 0.010) cases over the two-year period. The emergence and circulation of community-associated MRSA variants were observed in our hospital.