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Short-Term Success, Long-Term Failure: Strain Turnover and Virulence Re-Emergence May Drive Relapse in Pouchitis.

BACKGROUND & AIMS: Pouchitis, de-novo small intestinal inflammation is the most common complication developing in patients with ulcerative colitis after total large bowel resection and ileal pouch-anal anastomosis (IPAA) reconstruction. While the first line treatment is antibiotics, the microbial properties underlying flare, remission, and relapse remain vague. We aimed to investigate how antibiotic treatment drives microbial shifts that underlie remission and contribute to relapse. METHODS: Patients after IPAA were prospectively recruited during clinical flare (active pouchitis defined by the pouchitis disease activity index) and received a two-week course of metronidazole with either ciprofloxacin or doxycycline. Longitudinal follow up was conducted during a year. Clinical data were recorded, and fecal samples were obtained during consequent flares, recovery, and relapses. Microbial gene repertoire, strains, and resistance to antibiotics were determined. Metagenomic sequencing was integrated with whole-genome sequencing of Escherichia coli isolates, providing strain-specific virulence and antibiotic resistance profiles. RESULTS: Patients (n=21) recruited provided 130 samples over one-year follow-up. Both antibiotic regimens induced rapid but transient clinical improvement, reflected by a decrease in fecal calprotectin (728 to 265 &#x3bc;g/g, p<.05), and a marked reduction in bacterial exotoxin genes (p<.05), yet both parameters rebounded by 6 weeks post-treatment. Antibiotic resistance gene abundance significantly increased during treatment (p<.05), without expansion of resistance gene diversity, indicating that pre-existing resistant strains increased. CONCLUSIONS: Antibiotic-induced remission in pouchitis likely results from a temporary suppression of exotoxin-producing bacteria, enabling resistant, low-virulence strains to transiently dominate; The fact that harmful strains quickly rebound after treatment cessation highlights the need for targeted approaches to achieve sustained microbial control.

Inflammatory bowel disease

A comparative analysis of the clinical and genomic characteristics of Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus in Korea and Japan.

Panton-Valentine leukocidin (PVL) is a leukocyte-lytic toxin produced by Staphylococcus aureus, which is primarily associated with skin and soft tissue infections. Notably, there has been an increase in the number of cases caused by the USA300 lineage in Japan. However, the reported prevalence of USA300 is limited in other Asian countries, including Korea. This study investigated the prevalence of PVL-positive methicillin-resistant S. aureus (MRSA) in Korea and Japan and compared their molecular epidemiological characteristics. A total of 463 MRSA strains were analyzed, comprising 283 strains from patients visiting two hospitals in Seongnam and Seoul, Korea, and 180 strains from six hospitals in Tokyo, Japan, between 2018 and 2019. The PVL-encoding genes lukS/F-PV were detected using PCR. Molecular epidemiological and phylogenetic analyses were performed using next-generation sequencing. Overall, 27 (9.5%) PVL-positive MRSA strains were detected among strains isolated from Korea, and 16 (8.9%) were detected among those isolated from Japan. Genotyping of PVL-positive strains revealed that 85.2% of Korean and 81.3% of Japanese strains belonged to USA300. Most USA300 strains from Japan and Korea formed distinct clusters in phylogenetic analyses. Meanwhile, &#x3a8;USA300 and ST22-PT, clones that are prevalent in Japan, were isolated in Korea. This study showed that USA300 strains, which are becoming more prevalent in Japan, are also present in Korea. Furthermore, this study suggests that &#x3a8;USA300 and ST22-PT may be spreading between these two countries. Therefore, it is necessary to continue monitoring the epidemiological trends of PVL-positive MRSA clones both domestically and internationally.IMPORTANCEPanton-Valentine leukocidin (PVL) is a major toxin produced by Staphylococcus aureus. Although a rapid increase in PVL-positive strains has been reported in Japan, data on PVL-positive strains in Korea remain limited. In this study, we performed a comparative analysis of PVL-positive S. aureus isolates from Korea and Japan. The results showed that the clinical backgrounds and genetic profiles of PVL-positive strains isolated in Korea and Japan were highly similar. Furthermore, we confirmed for the first time that clones circulating in Japan, including &#x3a8;USA300 and ST22-PT, were also isolated in Korea. These findings provide valuable insights into the epidemiological status of PVL-positive S. aureus in East Asia.

Leukocidins

Genomic detection of Panton-Valentine Leucocidins encoding genes, virulence factors and distribution of antiseptic resistance determinants among Methicillin-resistant S. aureus isolates from patients attending regional referral hospitals in Tanzania.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a formidable public scourge causing worldwide mild to severe life-threatening infections. The ability of this strain to swiftly spread, evolve, and acquire resistance genes and virulence factors such as pvl genes has further rendered this strain difficult to treat. Of concern, is a recently recognized ability to resist antiseptic/disinfectant agents used as an essential part of treatment and infection control practices. This study aimed at detecting the presence of pvl genes and determining the distribution of antiseptic resistance genes in Methicillin-resistant Staphylococcus aureus isolates through whole genome sequencing technology. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted across six regional referral hospitals-Dodoma, Songea, Kitete-Kigoma, Morogoro, and Tabora on the mainland, and Mnazi Mmoja from Zanzibar islands counterparts using the archived isolates of Staphylococcus aureus bacteria. The isolates were collected from Inpatients and Outpatients who attended these hospitals from January 2020 to Dec 2021. Bacterial analysis was carried out using classical microbiological techniques and whole genome sequencing (WGS) using the Illumina Nextseq 550 sequencer platform. Several bioinformatic tools were used, KmerFinder 3.2 was used for species identification, MLST 2.0 tool was used for Multilocus Sequence Typing and SCCmecFinder 1.2 was used for SCCmec typing. Virulence genes were detected using virulenceFinder 2.0, while resistance genes were detected by ResFinder 4.1, and phylogenetic relatedness was determined by CSI Phylogeny 1.4 tools. RESULTS: Out of the 80 MRSA isolates analyzed, 11 (14%) were found to harbor LukS-PV and LukF-PV, pvl-encoding genes in their genome; therefore pvl-positive MRSA. The majority (82%) of the MRSA isolates bearing pvl genes were also found to exhibit the antiseptic/disinfectant genes in their genome. Moreover, all (80) sequenced MRSA isolates were found to harbor SCCmec type IV subtype 2B&5. The isolates exhibited 4 different sequence types, ST8, ST88, ST789 and ST121. Notably, the predominant sequence type among the isolates was ST8 72 (90%). CONCLUSION: The notably high rate of antiseptic resistance particularly in the Methicillin-resistant S. aureus strains poses a significant challenge to infection control measures. The fact that some of these virulent strains harbor the LukS-PV and LukF-PV, the pvl encoding genes, highlight the importance of developing effective interventions to combat the spreading of these pathogenic bacterial strains. Certainly, strengthening antimicrobial resistance surveillance and stewardship will ultimately reduce the selection pressure, improve the patient's treatment outcome and public health in Tanzania.

Methicillin-Resistant Staphylococcus aureus

Molecular epidemiology of panton valentine leukocidin-producing Staphylococcus aureus infections, Djibouti, 2018-2023.

Between 2018 and 2023, a genomic study was conducted in a military camp in Djibouti to investigate the molecular epidemiology of Panton-Valentine Leukocidin-producing Staphylococcus aureus. Among 43 isolates, Sequence Type 152 was predominant (72%), mainly associated with spa types t355 and t4235. Core-genome Multi-Locus Sequence Typing revealed two concurrent transmission dynamics: localized inter-human outbreaks and repeated introductions from external sources. Comparative genomics with other African Sequence Type 152 isolates showed similar levels of diversity, suggesting a widespread continental dissemination. These findings highlight the importance of genomic surveillance to better understand and control the spread of this virulent lineage in Africa.

Leukocidins