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At least 145 records · Page 8Linked to original sources
PubMed2000

The state of antibiotic resistance surveillance: an overview of existing activities and new strategies.

The growing global problem of antibiotic resistance requires a worldwide surveillance strategy to characterize the magnitude of the problem, guide clinical care decisions, and assess the impact of prevention and control interventions. Because many existing antibiotic resistance surveillance activities have developed independently of one another and vary greatly in their focus, key organizations are promoting strategies to standardize surveillance activities and build collaboration to promote effective global surveillance. With medical facilities operating throughout the world to support a highly mobile beneficiary population, the Department of Defense's Military Health System could benefit from partnership with civilian efforts to achieve global antibiotic resistance surveillance. This article's overview of existing surveillance activities and new strategies provides information requisite to the Department of Defense undertaking of development of a worldwide antibiotic resistance surveillance program to complement and integrate with civilian programs.

Centers for Disease Control and Prevention, U.S.↗
PubMed2003

The delicate balance of world health. Emerging plagues & resurrected pestilence. A report from the World Health Forum 1998.

The Health Industry Council and the International Hospital Federation welcomed an international audience of 21 participants from 13 countries to the third biannual World Health Forum (WHF). Participants in the WHF 1998 were nominated by their peers because of a distinguished professional record in their respective fields in their own nations. Countries represented included Belgium, Brazil, Chile, Greece, Hungary, India, Israel, Mexico, Nigeria, Sweden, Switzerland, Thailand, and the United States. The purpose of the event was to examine emerging and re-emerging infectious diseases from an international perspective, and to develop a set of guidelines and recommendations for proactively managing potential and recurring infectious disease outbreaks. This topic was chosen to provide an opportunity for different nations to come together and respond to the growing international public health threat posed by the increased proliferation of antibiotic-drug-resistant micro-organisms, food-borne illnesses, and emerging and re-emerging outbreaks of infectious diseases.

Communicable Diseases, Emerging↗
PubMed2004

CpG DNA induces IgG class switch DNA recombination by activating human B cells through an innate pathway that requires TLR9 and cooperates with IL-10.

TLRs are pattern recognition receptors that initiate innate immune responses. TLR9 detects microbial DNA with hypomethylated CpG motifs and in humans is preferentially expressed by IFN-alpha-producing plasmacytoid dendritic cells and B cells. In addition to favoring IFN-alpha release, TLR9 signals B cell activation, proliferation, and IgM production. Recent findings suggest that CpG DNA-TLR9 interaction plays a key role in systemic lupus erythematosus and rheumatoid arthritis, two autoimmune disorders characterized by dysregulated production of DNA-reactive IgG. We show that CpG DNA initiates germline C(gamma)1, C(gamma)2, and C(gamma)3 gene transcription by activating B cells through a TLR9-mediated NF-kappaB-Rel-dependent innate pathway that cooperates with IL-10 through STAT proteins and IFN-responsive factors. This pathway is inhibited by chloroquine, a drug that attenuates the clinical manifestations of IgG-mediated autoimmune disorders. Germline C(gamma) gene transcription is associated with up-regulation of activation-induced cytidine deaminase, a key element of the B cell class switch-inducing machinery, and is followed by class switch DNA recombination from C(micro) to C(gamma)1, C(gamma)2, and C(gamma)3. Subsequent IgG production requires additional signals from BCR and a B cell-activating factor of the TNF family (BAFF), produced by dendritic cells upon exposure to IFN-alpha. Our findings suggest that CpG DNA-TLR9 interaction may be important to initiate or amplify early T cell-independent IgG responses against pathogens. This implies that CpG DNA released during infections may exacerbate autoimmunity by stimulating autoreactive B cells to switch from an IgM to a more pathogenic IgG isotype.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Multivariate analysis of childhood microbial keratitis in South India.

INTRODUCTION: Corneal infection is the most common cause of profound ocular morbidity leading to blindness worldwide. Corneal infection in children is difficult to diagnose and treat, as they are unwilling and sometimes unable to cooperate during active management. This study analyses the prevalence, microbiology, demography, therapeutic and visual outcome of infectious microbial keratitis in the paediatric age group seen at a tertiary eye care hospital in south India. MATERIALS AND METHODS: A retrospective review of all cases presenting with keratitis to the ocular microbiology and cornea service at Aravind Eye Hospital, Coimbatore, from February 1997 to January 2004, was done to screen the patients for microbial keratitis. Their records were further analysed for clinical and microbiological details. Cases with culture-proven non-viral keratitis in children <or=15 years were included in the study. Full ophthalmic examination was performed for all cases. RESULTS: Of the 310 patients who attended the cornea clinic, 97 (31.2%) patients were confirmed to be positive for microbial keratitis. 54.6% of cases were male. The most common predisposing cause of ulceration was trauma (69%) with organic matter. Pure bacterial cultures were obtained from 64 (65.9%) eyes, whereas pure fungal cultures were obtained from 37 (38.1%) eyes. Four (4.1%) eyes showed mixed growth. CONCLUSION: The most commonly isolated organism was Pseudomonas aeruginosa. The most common predisposing cause of infectious microbial keratitis was corneal trauma. Early stage of diagnosis and formulation of an uncompromising management protocol can prevent profound visual morbidity.

Adolescent↗
PubMed2005

Microbial conversion of daunomycin wastes in unsteril soil inoculated with Bjerkandera adusta R59.

Effect of cooperation between native soil microorganisms and white-rot fungus Bjerkandera adusta R59 on degradation of daunomycin post-production wastes in soil was described. Pure cultures of B. adusta R59 strain were capable to decolorize and decompose that cytostatic xenobiotic in liquid media. Presence of R59 strain in studied daunomycin waste/soil systems increased the rate of the antibiotic conversion. The markers of that process were changes of waste biomass or daunomycin concentration (in pulp) and phenolics level and peroxidase activity (in effluent). It was shown that daunomycin in the wastes may be metabolized even up to 20% of its initial concentration. This effect was conjugated with the propagation of native soil microorganisms (microfungi and bacteria) more significant than in parallel system without R59 strain.

Antibiotics, Antineoplastic↗
PubMed1998

A swine model for the evaluation of efficacy of anti-microbial catheter coatings.

A swine model was developed to investigate the efficacy of percutaneous venous catheters with anti-microbial coatings. The catheters used in the study consisted of silver-coated and uncoated catheters, both designed for percutaneous venous access. Five commercial pigs were each implanted with three venous catheters and followed for a period of 90 days. Two of the three catheters were coated and one was uncoated. To evaluate the percutaneous aspects of the catheters in the model, two venous access catheters were implanted percutaneously, parallel to the dorsal midline. These catheters were just caudal to the region that is dorsal to the scapula in each animal. In each case, the catheter to the left of the dorsal midline was silver-coated while the catheter to the right of the dorsal midline was uncoated. A silver-coated catheter was also implanted in the left external jugular vein of each animal and buried subcutaneously in order to evaluate the elution of the coating through the body under venous contact. Over the 90 day period, the concentration of silver in the blood rose to a mean peak level of 23.2 ppb following implantation of the catheters and then decreased after the second post-surgery week. The histological evaluation and macroscopic inspection at necropsy revealed minimal tissue response to both coated and uncoated materials. Data on bacterial growth indicated that bacteria were present at the terminal subcutaneous end of two of the uncoated percutaneous catheters. Based upon serum silver levels, exudate formation, histological examination, and bacterial growth information, the swine model was deemed to be suitable for testing the efficacy of catheters containing anti-microbial coatings.

Animals↗
PubMed2003

Kinetic mechanism of the GCN5-related chromosomal aminoglycoside acetyltransferase AAC(6')-Ii from Enterococcus faecium: evidence of dimer subunit cooperativity.

The aminoglycoside 6'-N-acetyltransferase AAC(6')-Ii from Enterococcus faecium is an important microbial resistance determinant and a member of the GCN5-related N-acetyltransferase (GNAT) superfamily. We report here the further characterization of this enzyme in terms of the kinetic mechanism of acetyl transfer and identification of rate-contributing step(s) in catalysis, as well as investigations into the binding of both acetyl-CoA and aminoglycoside substrates to the AAC(6')-Ii dimer. Product and dead-end inhibition studies revealed that AAC(6')-Ii follows an ordered bi-bi ternary complex mechanism with acetyl-CoA binding first followed by antibiotic. Solvent viscosity studies demonstrated that aminoglycoside binding and product release govern the rate of acetyl transfer, as evidenced by changes in both the k(cat)/K(b) for aminoglycoside and k(cat), respectively, with increasing solvent viscosity. Solvent isotope effects were consistent with our viscosity studies that diffusion-controlled processes and not the chemical step were rate-limiting in drug modification. The patterns of partial and mixed inhibition observed during our mechanistic studies were followed up by investigating the possibility of subunit cooperativity in the AAC(6')-Ii dimer. Through the use of AAC-Trp(164) --> Ala, an active mutant which exists as a monomer in solution, the partial nature of the competitive inhibition observed in wild-type dead-end inhibition studies was alleviated. Isothermal titration calorimetry studies also indicated two nonequivalent antibiotic binding sites for the AAC(6')-Ii dimer but only one binding site for the Trp(164) --> Ala mutant. Taken together, these results demonstrate subunit cooperativity in the AAC(6')-Ii dimer, with possible relevance to other oligomeric members of the GNAT superfamily.

Acetyltransferases↗
PubMed2000

Evidence for an accessory protein function for Toll-like receptor 1 in anti-bacterial responses.

Members of the Toll-like receptor (TLR) family are components of the mammalian anti-microbial response, signaling with a domain closely related to that of IL-1 receptors. In this report the expression and function of TLR1, a TLR of unknown function, are examined. TLR1 is expressed by monocytes, as demonstrated using a novel mAb. Monocytes also express TLR2. TLR1 transfection of HeLa cells, which express neither TLR1 nor TLR2, was not sufficient to confer responsiveness to several microbial extracts. However, cotransfection of TLR1 and TLR2 resulted in enhanced signaling by HeLa cells to soluble factors released from Neisseria meningitidis relative to the response with either TLR alone. This phenomenon was also seen with high concentrations of some preparations of LPS. The N. meningitidis factors recognized by TLR1/TLR2 were not released by N. meningitidis mutant in the LpxA gene. Although LpxA is required for LPS biosynthesis, because cooperation between TLR1 and TLR2 was not seen with all LPS preparations, the microbial component(s) TLR1/2 recognizes is likely to be a complex of LPS and other molecules or a compound metabolically and chemically related to LPS. The functional IL-1R consists of a heterodimer; this report suggests a similar mechanism for TLR1 and TLR2, for certain agonists. These data further suggest that mammalian responsiveness to some bacterial products may be mediated by combinations of TLRs, suggesting a mechanism for diversifying the repertoire of Toll-mediated responses.

Acyltransferases↗