Biomedical subjects

Paul D Fey

Publications and source records attributed to Paul D Fey.

8 recordsLinked to original sources

PubMed2006

Vancomycin-intermediate Staphylococcus aureus strains have impaired acetate catabolism: implications for polysaccharide intercellular adhesin synthesis and autolysis.

The most common mechanism by which Staphylococcus aureus gains resistance to vancomycin is by adapting its physiology and metabolism to permit growth in the presence of vancomycin. Several studies have examined the adaptive changes occurring during the transition to vancomycin-intermediate resistance, leading to a model of vancomycin resistance in which decreased cell wall turnover and autolysis result in increased cell wall thickness and resistance to vancomycin. In the present study, we identified metabolic changes common to vancomycin-intermediate S. aureus (VISA) strains by assessing the metabolic and growth characteristics of two VISA strains (vancomycin MICs of 8 microg/ml) and two isogenic derivative strains with vancomycin MICs of 32 microg/ml. Interestingly, we observed the parental strains had impaired catabolism of nonpreferred carbon sources (i.e., acetate), and this impairment became more pronounced as vancomycin resistance increased. To determine if acetate catabolism impairment is common to VISA strains, we assessed the ability of VISA and vancomycin-sensitive S. aureus (VSSA) clinical isolates to catabolize acetate. As expected, a significantly greater percentage of VISA strains (71%) had impaired acetate catabolism relative to VSSA (8%). This is an important observation because staphylococcal acetate catabolism is implicated in growth yield and antibiotic tolerance and in regulating cell death and polysaccharide intercellular adhesin synthesis.

Acetates↗

PubMed2005

Clonal analysis of Staphylococcus epidermidis isolates carrying or lacking biofilm-mediating genes by multilocus sequence typing.

Staphylococcus epidermidis is part of the normal microflora of the human skin but is also a leading cause of device-associated infections in critically ill patients. Commensal and clinical S. epidermidis isolates differ in their ability to form biofilms on medical devices; the synthesis of biofilms is mediated by the icaADBC operon. Currently, the epidemiological relatedness between ica-positive and -negative isolates is not known; neither is it known whether the ica genes can spread to biofilm-negative strains through horizontal gene transfer. In this study, multilocus sequence typing (MLST) was employed for the clonal analysis of 118 S. epidermidis ica-positive and -negative strains. MLST revealed that the majority of ica-positive and -negative strains were closely related and formed a single clonal complex. Within this complex one sequence type (ST27) was identified which contained exclusively ica-positive isolates and represented the majority of clinical strains tested. ST27 and related ica-positive clones carried different SCCmec cassettes (conferring methicillin resistance) and the insertion sequence IS256. The findings suggest that the S. epidermidis infections analyzed in this report are mainly caused by a single clone (ST27) which occurs preferentially in hospitals and differs from clones in the community. It is hypothesized that the successful establishment of ST27 within nosocomial environments has been facilitated by the presence of genes encoding biofilm and resistance traits.

Bacterial Adhesion↗

PubMed2005

Beta-lactam resistance and Enterobacteriaceae, United States.

Extended-spectrum cephalosporins (ESC) are an important drug class for treating severe Salmonella infections. We screened the human collection from the National Antimicrobial Resistance Monitoring System 2000 for ESC resistance mechanisms. Of non-Typhi Salmonella tested, 3.2% (44/1,378) contained blaCMY genes. Novel findings included blaCMY-positive Escherichia coli O157:H7 and a blaSHV-positive Salmonella isolate. CMY-positive isolates showed a ceftriaxone MIC > or =2 microg/mL.

Cephalosporins↗

PubMed2004

Effect of silver-coated urinary catheters: efficacy, cost-effectiveness, and antimicrobial resistance.

BACKGROUND: Urinary tract infections (UTIs) are the most common nosocomial infection experienced by patients in United States hospitals and are responsible for significant morbidity and excess hospital costs. The purpose of this study was to determine the efficacy of a silver alloy, hydrogel-coated, urinary catheter in the prevention of catheter-associated UTI, to assess the cost effectiveness of the coated catheter, and to test for the emergence of silver-resistance in urinary microbial isolates. METHODS: A 2-year prospective surveillance study in 10 patient care units was conducted to determine the rate of catheter-associated UTI. Historic control data was utilized to assess the effect of the coated catheter. A cost-effectiveness analysis was conducted using a range of cost estimates. Silver susceptibility was determined for microbes responsible for catheter-associated UTI. RESULTS: Data were analyzed using a Poisson regression model. The rate of catheter-associated UTI fell from 6.13/1000 catheter-days during the period 1999-2000 to 2.62/1000 catheter-days during 2001-2002 ( P = .002). Calculated cost savings varied widely. Modest savings were achieved at the realistic lower cost estimates. No silver-resistant microbes were recovered in the susceptibility tests. CONCLUSIONS: The introduction of a silver alloy, hydrogel-coated urinary catheter was associated with a significant decline in nosocomial UTI and cost savings over the range of cost estimates. Silver-resistant urinary pathogens were not recovered from patients experiencing catheter-associated UTI during the study period.

Anti-Bacterial Agents↗

PubMed2004

Identification of common subpopulations of non-sorbitol-fermenting, beta-glucuronidase-negative Escherichia coli O157:H7 from bovine production environments and human clinical samples.

Non-sorbitol-fermenting, beta-glucuronidase-negative Escherichia coli O157:H7 strains are regarded as a clone complex, and populations from different geographical locations are believed to share a recent common ancestor. Despite their relatedness, high-resolution genotyping methods can detect significant genome variation among different populations. Phylogenetic analysis of high-resolution genotyping data from these strains has shown that subpopulations from geographically unlinked continents can be divided into two primary phylogenetic lineages, termed lineage I and lineage II, and limited studies of the distribution of these lineages suggest there could be differences in their propensity to cause disease in humans or to be transmitted to humans. Because the genotyping methods necessary to discriminate the two lineages are tedious and subjective, these methods are not particularly suited for studying the large sets of strains that are required to systematically evaluate the ecology and transmission characteristics of these lineages. To overcome this limitation, we have developed a lineage-specific polymorphism assay (LSPA) that can readily distinguish between the lineage I and lineage II subpopulations. In the studies reported here, we describe the development of a six-marker test (LSPA-6) and its validation in a side-by-side comparison with octamer-based genome scanning. Analysis of over 1,400 O157:H7 strains with the LSPA-6 demonstrated that five genotypes comprise over 91% of the strains, suggesting that these subpopulations may be widespread.

Animals↗

PubMed2003

Molecular epidemiology in the public health and hospital environments.

The increasing speed and ease of genomic sequencing coupled with available funding to sequence multiple, unrelated strains of the same species will lead inevitably to the identification of candidate genes that can be used as molecular typing tools (MLST, SLST, microarray approach). However, it is important to note that even the most sophisticated typing tool should never replace a full epidemiologic investigation in which all available information is taken into account. Nevertheless, the typing methods discussed in this article and those yet to be developed have significantly improved the quality of health care worldwide.

Bacterial Infections↗

PubMed2003

Monsel's solution: a potential vector for nosocomial infection?

Monsel's solution is a common topically applied hemostatic agent used in minor dermatologic and gynecologic surgery. Clinically, because it is often stored for long periods and dispensed from a common source for multiple patients, Monsel's solution is a potential vector for transmission of infection. However, microbiologic inoculation studies and contamination surveys indicate that Monsel's solution has properties that prohibit microbial growth, making it an unlikely vector for nosocomial infection.

Bacterial Infections↗

PubMed2003

Extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae: considerations for diagnosis, prevention and drug treatment.

Extended spectrum beta-lactamase (ESBL)-producing organisms pose unique challenges to clinical microbiologists, clinicians, infection control professionals and antibacterial-discovery scientists. ESBLs are enzymes capable of hydrolysing penicillins, broad-spectrum cephalosporins and monobactams, and are generally derived from TEM and SHV-type enzymes. ESBLs are often located on plasmids that are transferable from strain to strain and between bacterial species. Although the prevalence of ESBLs is not known, it is clearly increasing, and in many parts of the world 10-40% of strains of Escherichia coli and Klebsiella pneumoniae express ESBLs. ESBL-producing Enterobacteriaceae have been responsible for numerous outbreaks of infection throughout the world and pose challenging infection control issues. Clinical outcomes data indicate that ESBLs are clinically significant and, when detected, indicate the need for the use of appropriate antibacterial agents. Unfortunately, the laboratory detection of ESBLs can be complex and, at times, misleading. Antibacterial choice is often complicated by multi-resistance. Many ESBL-producing organisms also express AmpC beta-lactamases and may be co-transferred with plasmids mediating aminoglycoside resistance. In addition, there is an increasing association between ESBL production and fluoroquinolone resistance. Although in in vitro tests ESBLs are inhibited by beta-lactamase inhibitors such as clavulanic acid, the activity of beta-lactam/beta-lactamase inhibitor combination agents is influenced by the bacterial inoculum, dose administration regimen and specific type of ESBL present. Currently, carbapenems are regarded as the drugs of choice for treatment of infections caused by ESBL-producing organisms. Unfortunately, use of carbapenems has been associated with the emergence of carbapenem-resistant bacterial species such as Stenotrophomonas sp. or Pseudomonas sp.

Anti-Bacterial Agents↗