Dissemination of meticillin-resistant Staphylococcus aureus sequence type 8 (USA300) in Taiwan.

BACKGROUND: In Taiwan, sequence type (ST) 239 and ST59 were two major clones among meticillin-resistant Staphylococcus aureus (MRSA) clinical isolates in the past two decades. USA300 (ST8) prevailed in the Americas but not in outside areas. Recently USA300 (ST8) emerged and was increasingly identified in Taiwan; we thus conducted an island-wide study to explore the role of USA300 among MRSA isolates. METHODS: One hundred MRSA bloodstream isolates identified in 2020 from each of the six participating hospitals in Taiwan were collected and characterized. The first 10 ST8 isolates from each hospital were further analysed by whole-genome sequencing. RESULTS: Of the 590 confirmed MRSA isolates, a total of 22 pulsotypes and 21 STs were identified. The strain of pulsotype AI/ST8 was the most common lineage identified, accounting for 187 isolates (31.7%) and dominating in five of six hospitals, followed by pulsotype A/ST239 (14.7%), pulsotype C/ST59 (13.9%) and pulsotype D/ST59 (9.2%). Of the 187 pulsotype AI/ST8 isolates, 184 isolates were characterized as USA300 and clustered in three major sub-pulsotypes, accounting for 78%. Ninety per cent of the 60 ST8 isolates for whole-genome sequencing were clustered in three major clades. CONCLUSIONS: In 2020, USA300 became the most common clone of MRSA in Taiwan, accounting for >30% of MRSA bloodstream isolates island wide. Most of USA300 isolates circulating in Taiwan might have been imported on multiple occasions and evolved into at least three successful local clades. MRSA USA300 has successfully established its role in Taiwan, an area outside of the Americas.

J-2156, a small molecule somatostatin type 4 receptor agonist, alleviated hindpaw hypersensitivity in the streptozotocin-induced rat model of painful diabetic neuropathy but with a 2-fold decrease in potency at an advanced stage in the model, mimicking morphine.

There is a large unmet need for novel pain-killers to improve relief of painful diabetic neuropathy (PDN). Herein, we assessed the efficacy of the somatostatin type 4 (SST4) receptor agonist, J-2156, for relief of PDN in rats. Diabetes was induced with streptozotocin (STZ; 70 mg/kg) and bilateral hindpaw hypersensitivity was fully developed by 8-week post-STZ. In the intervals, 8-12-weeks (morphine-sensitive phase; Phase 1) and 16-18-weeks (morphine-hyposensitive phase; Phase 2) post-STZ, rats received a single dose of intraperitoneal (i.p.) J-2156 (10, 20, 30 mg/kg), gabapentin (100 mg/kg i.p.), subcutaneous morphine (1 mg/kg) or vehicle. Hindpaw withdrawal thresholds (PWTs) were assessed using von Frey filaments pre-dose and at regular intervals over 3-h post-dose. In Phase 1, J-2156 at 30 mg/kg evoked significant anti-allodynia in the hindpaws with maximal effect at 1.5 h compared with 1 h for gabapentin and morphine. The durations of action for all three compounds were greater than 3 h. The corresponding mean (±SEM) extent and duration of anti-allodynia (ΔPWT AUC) for gabapentin did not differ significantly from that for J-2156 (30 mg/kg) or morphine. However, in Phase 2, the ΔPWT AUC for morphine was reduced to approximately 25% of that in Phase 1, mirroring our previous work. Similarly, the mean (±SEM) ΔPWT AUC for J-2156 (30 mg/kg) in Phase 2 was approximately 45% of that for Phase 1 whereas for gabapentin the mean (±SEM) ΔPWT AUCs did not differ significantly (p > 0.05) between the two phases. Our findings further describe the preclinical pain relief profile of J-2156 and complement previous work in rat models of inflammatory pain, neuropathic pain and low back pain. SST4 receptor agonists hold promise as novel therapeutics for the relief of PDN, a type of peripheral neuropathic pain that is often intractable to relief with clinically used drug treatment options.