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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.


Zautner A.E.,Institute of Medical Microbiology | Krause M.,Otto Korner | Stropahl G.,University of Rostock | Holtfreter S.,University of Greifswald | And 5 more authors.
PLoS ONE | Year: 2010

Background: The two major indications for tonsillectomy are recurrent tonsillitis (RT) and peritonsillar abscess (PTA). Unlike PTAs, which are primarily treated surgically, RT is often cured by tonsillectomy only after a series of failed drug therapy attempts. Although the bacteriological background of RT has been studied, the reason for the lack of success of conservative therapeutic approaches is not well understood. Methods: In a prospective study, tonsil specimens from 130 RT patients and 124 PTA patients were examined for the presence of extra- and intracellular bacteria using antibiotic protection assays. Staphylococcus aureus isolates from RT patients were characterized by pulsed-field gel electrophoresis (PFGE), spa-typing and MSCRAMM-gene-PCR. Their ability for biofilm formation was tested and their cell invasiveness was confirmed by a flow cytometric invasion assay (FACS), fluorescent in situ hybridization (FISH) and immunohistochemistry. Findings: S. aureus was the predominant species (57.7%) in RT patients, whereas Streptococcus pyogenes was most prevalent (20.2%) in PTA patients. Three different assays (FACS, FISH, antibiotic protection assay) showed that nearly all RT-associated S. aureus strains were located inside tonsillar cells. Correspondingly, the results of the MSCRAMM-gene-PCRs confirmed that 87% of these S. aureus isolates were invasive strains and not mere colonizers. Based upon PFGE analyses of genomic DNA and on spa-gene typing the vast majority of the S. aureus isolates belonged to different clonal lineages. Conclusions: Our results demonstrate that intracellular residing S. aureus is the most common cause of RT and indicate that S. aureus uses this location to survive the effects of antibiotics and the host immune response. A German translation of the Abstract is provided as supplementary material (Abstract S1). © 2010 Zautner et al.


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.


Imirzalioglu C.,Institute of Medical Microbiology | Dahmen H.,Veterinary Practice | Hain T.,Institute of Medical Microbiology | Billion A.,Institute of Medical Microbiology | And 3 more authors.
Journal of Clinical Microbiology | Year: 2011

Mycobacterium avium subsp. paratuberculosis is the causative agent of Johne's disease (JD) in cattle and may be associated with Crohn's disease (CD) in humans. It is the slowest growing of the cultivable mycobacteria, and culture from clinical, veterinary, food, or environmental specimens can take 4 months or even longer. Currently, the insertion element IS900 is used to detect M. avium subsp. paratuberculosis DNA. However, closely related IS900 elements are also present in other mycobacteria, thus limiting its specificity as a target. Here we describe the use of novel primer sets derived from the sequences of two highly specific single copy genes, MAP2765c and MAP0865, for the quantitative detection of M. avium subsp. paratuberculosis within 6 h by using real-time PCR. Specificity of the target was established using 40 M. avium subsp. paratuberculosis isolates, 67 different bacterial species, and two intestinal parasites. Using the probes and methods described, we detected 27 (2.09%) M. avium subsp. paratuberculosis-positive stool specimens from 1,293 individual stool samples by the use of either IS900 or probes deriving from the MAP2765c and MAP0865 genes described here. In general, bacterial load due to M. avium subsp. paratuberculosis was uniformly low in these samples and we estimated 500 to 5,000 M. avium subsp. paratuberculosis bacteria per gram of stool in assay-positive samples. Thus, the methods described here are useful for rapid and specific detection of M. avium subsp. paratuberculosis in clinical samples. Copyright © 2011, American Society for Microbiology. All Rights Reserved.


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.


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.


Aibinu I.,University of Lagos | Aibinu I.,Institute of Medical Microbiology | Odugbemi T.,University of Lagos | Koenig W.,Institute of Medical Microbiology | Ghebremedhin B.,Institute of Medical Microbiology
Clinical Microbiology and Infection | Year: 2012

Of 109 clinical Escherichia coli isolates from two major tertiary hospitals in Lagos (University Teaching Hospital and the National Orthopaedic Hospital Igbobi), 14 (12.8%) extended-spectrum beta-lactamse (ESBL) producers were characterized using PCR and sequencing, ERIC-PCR and multilocus sequence typing. All ESBL-producing isolates encoded only the CTX-M-15 gene. Clonal group ST131 (35.7%) was the predominant ST, followed by ST617 (28.6%). Isolated cases of other sequence types were also observed. Plasmid-mediated quinolone resistance genes qnrA, qnrB1 and aac-(6′)-lb-cr were detected among these ESBL isolates of different clonal groups. This is the first description of the clonality of CTX-M-15-producing E. coli from Nigeria. The presence of diverse clonal lineages shows the continuing potential for genetic diversification and emergence of new epidemic strains. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.


Manetti A.G.O.,Novartis | Koller T.,Institute of Medical Microbiology | Becherelli M.,Novartis | Buccato S.,Novartis | And 4 more authors.
PLoS ONE | Year: 2010

Group A Streptococcus (GAS, Streptococcus pyogenes) is a Gram-positive human pathogen responsible for a diverse variety of diseases, including pharyngitis, skin infections, invasive necrotizing fasciitis and autoimmune sequelae. We have recently shown that GAS cell adhesion and biofilm formation is associated with the presence of pili on the surface of these bacteria. GAS pilus proteins are encoded in the FCT (Fibronectin- Collagen-T antigen) genomic region, of which nine different variants have been identified so far. In the present study we undertook a global analysis of GAS isolates representing the majority of FCT-variants to investigate the effect of environmental growth conditions on their capacity to form multicellular communities. For FCT-types 2, 3, 5 and 6 and a subset of FCT-4 strains, we observed that acidification resulting from fermentative sugar metabolism leads to an increased ability of the bacteria to form biofilm on abiotic surfaces and microcolonies on epithelial cells. The higher biofilm forming capacity at low environmental pH was directly associated with an enhanced expression of the genes encoding the pilus components and of their transcription regulators. The data indicate that environmental pH affects the expression of most pilus types and thereby the formation of multicellular celladhering communities that assist the initial steps of GAS infection. © 2010 Manetti et al.


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.


Imohl M.,Institute of Medical Microbiology | Imohl M.,RWTH Aachen | Reinert R.R.,Institute of Medical Microbiology | Ocklenburg C.,RWTH Aachen | Van Linden M.D.,Institute of Medical Microbiology
Journal of Clinical Microbiology | Year: 2010

A total of 7,764 isolates from patients with invasive pneumococcal disease (IPD) were collected from 1992 to June 2006. Data on serotypes were available for 5,022 isolates (64.7% of all invasive isolates). Some 54.0% of the isolates originated from adults 216 years of age, and 46.0% were from children <16 years of age. The leading serotypes were 14, 23F, 1, 6B, 7F, 3, and 4. The serotypes significantly more common in children were 14, 6B, 19F, and 18C, while among adults, serotypes 3 and 4 were predominant. Serotype 7F was statistically more prevalent among children <4 months old than among the other age groups. Among children aged &4 months and <1 year, serotype 19F occurred statistically more frequently; and among children aged Sl year to <5 years, serotypes 14, 6B, and 18C were overrepresented. The serotypes predominantly affecting patients younger than the remaining collective of patients were 14, 6B, 19F, and 18C, while patients with IPD caused by serotypes 3, 4, and 9V were older than the collective, on average. Copyright © 2010, American Society for Microbiology. All Rights Reserved.

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