Browsing by Subject "VANCOMYCIN"

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  • Sivaranjani, Murugesan; Leskinen, Katarzyna; Aravindraja, Chairmandurai; Saavalainen, Päivi; Pandian, Shunmugiah Karutha; Skurnik, Mikael; Ravi, Arumugam Veera (2019)
    Background: Alpha-mangostin (alpha-MG) is a natural xanthone reported to exhibit rapid bactericidal activity against Gram-positive bacteria, and may therefore have potential clinical application in healthcare sectors. This study sought to identify the impact of alpha-MG on Staphylococcus epidermidis RP62A through integrated advanced omic technologies. Methods: S. epidermidis was challenged with sub-MIC (0.875 mu g/ml) of alpha-MG at various time points and the differential expression pattern of genes/proteins were analyzed in the absence and presence of alpha-MG using RNA sequencing and LC-MS/MS experiments. Bioinformatic tools were used to categorize the biological processes, molecular functions and KEGG pathways of differentially expressed genes/proteins. qRT-PCR was employed to validate the results obtained from these analyses. Results: Transcriptomic and proteomic profiling of alpha-MG treated cells indicated that genes/proteins affected by alpha-MG treatment were associated with diverse cellular functions. The greatest reduction in expression was observed in transcription of genes conferring cytoplasmic membrane integrity (yidC2, secA and mscL), cell division (ftsY and divlB), teichoic acid biosynthesis (tagG and dltA), fatty-acid biosynthesis (accB, accC, fabD, fabH, fabl, and fabZ), biofilm formation (icaA) and DNA replication and repair machinery (polA, polC, dnaE, and uvrA). Those with increased expression were involved in oxidative (katA and sodA) and cellular stress response (clpB, clpC, groEL, and asp23). The qRT-PCR analysis substantiated the results obtained from transcriptomic and proteomic profiling studies. Conclusion: Combining transcriptomic and proteomic methods provided comprehensive information about the antibacterial mode of action of alpha-MG. The obtained results suggest that alpha-MG targets S. epidermidis through multifarious mechanisms, and especially prompts that loss of cytoplasmic membrane integrity leads to rapid onset of bactericidal activity.
  • Raulinaitis, Vytas; Tossavainen, Helena; Aitio, Olli; Juuti, Jarmo T.; Hiramatsu, Keiichi; Kontinen, Vesa; Permi, Perttu (2017)
    We introduce LytU, a short member of the lysostaphin family of zinc-dependent pentaglycine endopeptidases. It is a potential antimicrobial agent for S. aureus infections and its gene transcription is highly upregulated upon antibiotic treatments along with other genes involved in cell wall synthesis. We found this enzyme to be responsible for the opening of the cell wall peptidoglycan layer during cell divisions in S. aureus. LytU is anchored in the plasma membrane with the active part residing in the periplasmic space. It has a unique Ile/Lys insertion at position 151 that resides in the catalytic site-neighbouring loop and is vital for the enzymatic activity but not affecting the overall structure common to the lysostaphin family. Purified LytU lyses S. aureus cells and cleaves pentaglycine, a reaction conveniently monitored by NMR spectroscopy. Substituting the cofactor zinc ion with a copper or cobalt ion remarkably increases the rate of pentaglycine cleavage. NMR and isothermal titration calorimetry further reveal that, uniquely for its family, LytU is able to bind a second zinc ion which is coordinated by catalytic histidines and is therefore inhibitory. The pH-dependence and high affinity of binding carry further physiological implications.
  • Forsblom, Erik; Ruotsalainen, Eeva; Jarvinen, Asko (2015)
    Introduction Rifampicin has been used as adjunctive therapy in Staphylococcus aureus bacteraemia (SAB) with a deep infection focus. However, data for prognostic impact of rifampicin therapy is unestablished including the optimal initiation time point. We studied the impact of rifampicin therapy and the optimal initiation time for rifampicin treatment on prognosis in methicillin-sensitive S. aureus bacteraemia with a deep infection. Methods Retrospective, multicentre study in Finland including 357 SAB patients with a deep infection focus. Patients with alcoholism, liver disease or patients who died within 3 days were excluded. Patients were categorised according to duration of rifampicin therapy and according to whether rifampicin was initiated early (within 7 days) or late (7 days after) after the positive blood cultures. Primary end point was 90 days mortality. Results Twenty-seven percent of patients received no rifampicin therapy, 14% received rifampicin for 1-13 days whereas 59% received rifampicin >= 14 days. The 90 day mortality was; 26% for patients treated without rifampicin, 16% for rifampicin therapy of any length and 10% for early onset rifampicin therapy >= 14 days. Lack of rifampicin therapy increased (OR 1.89, p=0.026), rifampicin of any duration decreased (OR 0.53, p=0.026) and rifampicin therapy >= 14 days with early onset lowered the risk for a fatal outcome (OR 0.33, p Conclusion Rifampicin adjunctive therapy for at least 14 days and initiated within 7 days of positive blood culture associated with improved outcome among SAB patients with a deep infection.
  • Oksi, Jarmo; Aalto, A.; Saila, P.; Partanen, T.; Anttila, Veli-Jukka A; Mattila, E. (2019)
    Reports on real-world experience on efficacy of bezlotoxumab (BEZ) has been lacking thus far. We retrospectively studied the efficacy and safety of BEZ in preventing the recurrence of Clostridium difficile infection (CDI) in five university hospitals in Finland. Seventy-three percent of our 46 patients remained free of recurrence in the following 3 months and the performance remained as 71% effective also among immunocompromised patients. In severe CDI, BEZ prevented recurrence in 63% of cases. From our study patients, 78% had three or more known risk factors for recurrence of CDI. Eight of our patients were waiting for fecal microbiota transplantation but after stopping the antibiotics that were continued to prevent recurrence of CDI and after receiving BEZ, all remained free of recurrence and did not need the procedure. Success with BEZ as an adjunctive treatment in preventing recurrence of CDI in high-risk patients may be rated as high. Among a subgroup of our patients, those already evaluated to be in need of fecal microbiota transplantation, BEZ seems to be an alternative option.
  • Ianiro, Gianluca; Mullish, Benjamin H.; Kelly, Colleen R.; Kassam, Zain; Kuijper, Ed J.; Ng, Siew C.; Iqbal, Tariq H.; Allegretti, Jessica R.; Bibbo, Stefano; Sokol, Harry; Zhang, Faming; Fischer, Monika; Costello, Samuel Paul; Keller, Josbert J.; Masucci, Luca; van Prehn, Joffrey; Quaranta, Gianluca; Quraishi, Mohammed Nabil; Segal, Jonathan; Kao, Dina; Satokari, Reetta; Sanguinetti, Maurizio; Tilg, Herbert; Gasbarrini, Antonio; Cammarota, Giovanni (2020)
    The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.
  • Forsblom, E.; Nurmi, A.-M.; Ruotsalainen, E.; Järvinen, A. (2016)
    The purpose of this study was to examine the prognostic impact of corticosteroids in hemodynamically stabile Staphylococcus aureus bacteremia (SAB). There were 361 hemodynamically stabile methicillin-sensitive SAB patients with prospective follow-up and grouping according to time-point, dose and indication for corticosteroid therapy. To enable analyses without external interfering corticosteroid therapy all patients with corticosteroid therapy equivalent to prednisone > 10 mg/day for >= 1 month prior to positive blood culture results were excluded. Twenty-five percent (92) of patients received corticosteroid therapy of which 11 % (40) had therapy initiated within 1 week (early initiation) and 9 % (31) had therapy initiated 2-4 weeks after (delayed initiation) positive blood culture. Twenty-one patients (6 %) had corticosteroid initiated after 4 weeks and were not included in the analyses. A total of 55 % (51/92) received a weekly prednisone dose > 100 mg. Patients with early initiated corticosteroid therapy had higher mortality compared to patients treated without corticosteroid therapy at 28 days (20 % vs. 7 %) (OR, 3.11; 95% CI, 1.27-7.65; p <0.05) and at 90 days (30 % vs. 10 %) (OR, 4.01; 95% CI, 1.82-8.81; p <0.001). Considering all prognostic markers, early initiated corticosteroid therapy predicted 28-day (HR, 3.75; 95% CI, 1.60-8.79; p = 0.002) and 90-day (HR, 3.10; 95% CI, 1.50-6.39; p = 0.002) mortality in Cox proportional hazards regression analysis. When including only patients receiving early initiated corticosteroid therapy with prednisone >= 100 mg/week the negative prognostic impact on 28-day mortality was accentuated (HR 4.8, p = 0.001). Corticosteroid therapy initiation after 1 week of positive blood cultures had no independent prognostic impact. Early initiation of corticosteroid therapy may be associate to increased mortality in hemodynamically stabile SAB.
  • Forsblom, E.; Tielinen, I.; Ruotsalainen, E.; Jarvinen, A. (2017)
    The prognostic impact of thrombocytopaenia in Staphylococcus aureus bacteraemia (SAB) has previously been determined at bacteraemia onset only and relevant pre-bacteraemic thrombocytopaenia predisposing parameters have not been accounted for. We evaluated the prognostic impact of low thrombocyte count in SAB excluding pre-bacteraemic factors potentially causing thrombocytopaenia. This was a multicentre retrospective analysis of methicillin-sensitive SAB (MS-SAB) patients. Thrombocyte count was determined at blood culture collection and at days 3 and 7. Thrombocytopae nia was defined as a thrombocyte count less than 150 x 10(9)/L. Patients with chronic alcoholism, liver diseases and haematologic malignancies were excluded. Altogether, 495 patients were identified. Thrombocytopaenia at blood culture and at day 3 associated to endocarditis (p <0.05 and p <0.01) and defervescence (p <0.001 and p <0.01). Mortality at 90 days was higher for patients with thrombocytopaenia at blood culture collection (26 vs. 16%, p <0.05), at day 3 (32 vs. 13%, p <0.01) and at day 7 (50 vs. 14%, p <0.001). In receiver operating characteristic analyses, thrombocytopaenia predicted a poor outcome at blood culture collection (p <0.05), at day 3 (p <0.001) and at day 7 (p <0.001). When accounting for all prognostic parameters, thrombocytopaenia at day 3 [hazard ratio (HR), 1.83; p = 0.05] demonstrated a trend towards poor outcome, whereas thrombocytopaenia at day 7 (HR, 3.64; p <0.001) associated to poor outcome. Thrombocytopaenia at blood culture collection was not a prognostic parameter when all prognostic factors were taken into account. However, thrombocytopaenia at day 3 indicated a poor outcome and thrombocytopaenia at day 7 was a significant independent negative prognostic marker that has not been previously reported in SAB.