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Recent studies in murine models of Staphylococcus aureus (S. aureus) infection have investigated the association of Toll-like receptor (TLR)2, TLR4, myeloid differentiation factor 88 (MyD88) and Nod-like receptor (NOD)2 with the production of cytokines / chemokines and their involvement in the recruitment of neutrophils, which mediate innate immune responses at infection sites. The availability of gene-knockout mice provided opportunities to analyze the redundant roles for specific recognition receptors in our understanding of the innate immune responses which contribute to staphylococcal disease pathogenesis. Emerging findings reveal that the role of recognition receptors in the innate host immune defense and inflammation elicited during infection is influenced both by the nature of S. aureus-associated pathogen-associated molecular patterns (PAMPs) and the site of infection highlighting the complex nature of these in vivo interactions. Different susceptibilities have been observed in the various gene-knockout mice regarding clinically relevant infection models. This review details ou current knowledge and indicates that further studies are needed to elucidate the contribution of TLR- / NLR-signaling at different sites of staphylococcal infection.

Mawalla B.,Health Science University | Mshana S.E.,Health Science University | Chalya P.L.,Health Science University | Imirzalioglu C.,Institute of Medical Microbiology | Mahalu W.,Health Science University
BMC Surgery | Year: 2011

Background: Surgical site infection (SSI) continues to be a major source of morbidity and mortality in developing countries despite recent advances in aseptic techniques. There is no baseline information regarding SSI in our setting therefore it was necessary to conduct this study to establish the prevalence, pattern and predictors of surgical site infection at Bugando Medical Centre Mwanza (BMC), Tanzania. Methods. This was a cross-sectional prospective study involving all patients who underwent major surgery in surgical wards between July 2009 and March 2010. After informed written consent for the study and HIV testing, all patients who met inclusion criteria were consecutively enrolled into the study. Pre-operative, intra-operative and post operative data were collected using standardized data collection form. Wound specimens were collected and processed as per standard operative procedures; and susceptibility testing was done using disc diffusion technique. Data were analyzed using SPSS software version 15 and STATA. Results: Surgical site infection (SSI) was detected in 65 (26.0%) patients, of whom 56 (86.2%) and 9 (13.8%) had superficial and deep SSI respectively. Among 65 patients with clinical SSI, 56(86.2%) had positive aerobic culture. Staphylococcus aureus was the predominant organism 16/56 (28.6%); of which 3/16 (18.8%) were MRSA. This was followed by Escherichia coli 14/56 (25%) and Klebsiella pneumoniae 10/56 (17.9%). Among the Escherichia coli and Klebsiella pneumoniae isolates 9(64.3%) and 8(80%) were ESBL producers respectively. A total of 37/250 (14.8%) patients were HIV positive with a mean CD4 count of 296 cells/ml. Using multivariate logistic regression analysis, presence of pre-morbid illness (OR = 6.1), use of drain (OR = 15.3), use of iodine alone in skin preparation (OR = 17.6), duration of operation 3 hours (OR = 3.2) and cigarette smoking (OR = 9.6) significantly predicted surgical site infection (SSI). Conclusion: SSI is common among patients admitted in surgical wards at BMC and pre-morbid illness, use of drain, iodine alone in skin preparation, prolonged duration of the operation and cigarette smoking were found to predict SSI. Prevention strategies focusing on factors associated with SSI is necessary in order to reduce the rate of SSI in our setting. © 2011 Mawalla et al; licensee BioMed Central Ltd.

Gould I.M.,Royal Infirmary | David M.Z.,University of Chicago | Esposito S.,The Second University of Naples | Garau J.,Hospital Universitari Mutua Of Terrassa | And 2 more authors.
International Journal of Antimicrobial Agents | Year: 2012

Meticillin-resistant Staphylococcus aureus (MRSA) remains one of the principal multiply resistant bacterial pathogens causing serious healthcare-associated and community-onset infections. This paper reviews recent studies that have elucidated the virulence strategies employed by MRSA, key clinical trials of agents used to treat serious MRSA infections, and accumulating data regarding the implications of antibacterial resistance in MRSA for clinical success during therapy. Recent pre-clinical data support a species-specific role for Panton-Valentine leukocidin in the development of acute severe S. aureus infections and have elucidated other virulence mechanisms, including novel modes of internalisation, varying post-invasion strategies (featuring both upregulation and downregulation of virulence factors) and phenotypic switching. Recent double-blind, randomised, phase III/IV clinical trials have demonstrated the efficacy of linezolid and telavancin in hospital-acquired pneumonia (HAP) and complicated skin and skin-structure infections (cSSSIs) caused by MRSA. Tigecycline was non-inferior to imipenem/cilastatin in non-ventilator-associated HAP but was inferior in ventilator-associated pneumonia and has shown a higher rate of death than comparators on meta-analysis. Ceftaroline was clinically and microbiologically non-inferior to vancomycin/aztreonam in the treatment of MRSA cSSSI. Key resistance issues include a rise in vancomycin minimum inhibitory concentrations in MRSA, reports of clonal isolates with linezolid resistance mediated by acquisition of the chloramphenicol/florfenicol resistance gene, and case reports of daptomycin resistance resulting in clinical failure. Novel antimicrobial targets must be identified with some regularity or we will face the risk of untreatable S. aureus infections. © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Pan B.,Nanjing University of Technology | Huang R.-Z.,Institute of Medical Microbiology | Han S.-Q.,Nanjing University of Technology | Qu D.,Institute of Medical Microbiology | And 3 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2010

A series of novel 2-arylimino-3-aryl-thiazolidine-4-ones was designed, synthesized and tested for in vitro antibiofilm activity against Staphylococcus epidermidis. Among them tested, some compounds with carboxylic acid groups showed good antibiofilm activity. The antibiofilm concentration of 1x was 6.25 μM. The structure-activity relationships revealed that incorporation of 2-phenylfuran moiety could greatly enhance antibiofilm activity of thiazolidine-4-one. © 2010 Elsevier Ltd. All rights reserved.

Mshana S.E.,Health Science University | Imirzalioglu C.,Institute of Medical Microbiology | Hain T.,Institute of Medical Microbiology | Domann E.,Institute of Medical Microbiology | And 2 more authors.
Clinical Microbiology and Infection | Year: 2011

The molecular epidemiology of 32 non-duplicate, CTX-M-15 extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli strains, isolated from clinical samples, was investigated. Multilocus sequence typing revealed multiple sequence type clonal complexes: ST131 (12), ST405 (4), ST638 (3), ST38 (2), ST827 (2), ST224 (1), ST648 (1), ST46 (1) and two new sequence type clonal complexes (1845 and 1848) in 22 pulsed field gel electrophoresis clusters. The blaCTX-M-15 gene was located on conjugative IncF plasmids. This is the first report of the worldwide emerging clonal complex ST131 linked to blaCTX-M-15 in Tanzania and demonstrates the need for constant surveillance in developing countries to prevent the spread of these multiresistant isolates. © 2011 European Society of Clinical Microbiology and Infectious Diseases.

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