Integration of molecular characterization of microorganisms in a global antimicrobial resistance surveillance program

© 2001 by the Infectious Diseases Society of America. All rights reserved.The SENTRY Antimicrobial Surveillance Program has incorporated molecular strain typing and resistance genotyping as a means of providing additional information that may be useful for understanding pathogenic microorganisms worldwide. Resistance phenotypes of interest include multidrug-resistant pathogens, extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, and fluoroquinolone-resistant (FQR) strains of gram-negative bacilli and Streptococcus pneumoniae. Clusters of 2 isolates within a given resistance profile that are linked temporally and by hospital location are flagged for DNA fingerprinting. Further characterization of organisms with respect to resistance genotype is accomplished with use of polymerase chain reaction and DNA sequencing. This process has been highly successful in identifying clonal spread within clusters of multiresistant pathogens. Between 50% and 90% of MRSA clusters identified by phenotypic screening contained evidence of clonal spread. Among the Enterobacteriaceae, ESBL-producing strains of Escherichia coli and Klebsiella pneumoniae are the most common pathogens causing clusters of infection, and 50% of recognized clusters demonstrate clonal spread. Clusters of Pseudomonas aeruginosa, Acinetobacter species, and Stenotrophomonas maltophilia have been noted with clonal spread among patients with urinary tract, respiratory, and bloodstream infections. Characterization of mutations in the FQR-determining region of phenotypically susceptible isolates of E. coli and S. pneumoniae has identified first-stage mutants among as many as 40% of isolates. The ability to characterize organisms phenotypically and genotypically is extremely powerful and provides unique information that is important in a global antimicrobial surveillance program.M. A. Pfaller, J. Acar, R. N. Jones, J. Verhoef, J. Turnidge, and H. S. Sade

Cost-Effectiveness of Preoperative Screening and Eradication of Staphylococcus aureus Carriage

BACKGROUND: Preoperative screening for nasal S. aureus carriage, followed by eradication treatment of identified carriers with nasal mupirocine ointment and chlorhexidine soap was highly effective in preventing deep-seated S. aureus infections. It is unknown how cost-effectiveness of this intervention is affected by suboptimal S. aureus screening. We determined cost-effectiveness of different preoperative S. aureus screening regimes. METHODS: We compared different screening scenarios (ranging from treating all patients without screening to treating only identified S. aureus carriers) to the base case scenario without any screening and treatment. Screening and treatment costs as well as costs and mortality due to deep-seated S. aureus infection were derived from hospital databases and prospectively collected data, respectively. RESULTS: As compared to the base case scenario, all scenarios are associated with improved health care outcomes at reduced costs. Treating all patients without screening is most cost-beneficial, saving €7339 per life year gained, as compared to €3330 when only identified carriers are treated. In sensitivity analysis, outcomes are susceptible to the sensitivity of the screening test and the efficacy of treatment. Reductions in these parameters would reduce the cost-effectiveness of scenarios in which treatment is based on screening. When only identified S. aureus carriers are treated costs of screening should be less than €6.23 to become the dominant strategy. CONCLUSIONS: Preoperative screening and eradication of S. aureus carriage to prevent deep-seated S. aureus infections saves both life years and medical costs at the same time, although treating all patients without screening is the dominant strategy, resulting in most health gains and largest savings

Species-selective killing of bacteria by antimicrobial peptide-PNAs

This is an open-access article distributed under the terms of the Creative Commons Attribution License, CC BY 4.0 which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Broad-spectrum antimicrobials kill indiscriminately, a property that can lead to negative clinical consequences and an increase in the incidence of resistance. Species-specific antimicrobials that could selectively kill pathogenic bacteria without targeting other species in the microbiome could limit these problems. The pathogen genome presents an excellent target for the development of such antimicrobials. In this study we report the design and evaluation of species-selective peptide nucleic acid (PNA) antibacterials. Selective growth inhibition of B. subtilis, E. coli, K. pnuemoniae and S. enterica serovar Typhimurium in axenic or mixed culture could be achieved with PNAs that exploit species differences in the translation initiation region of essential genes. An S. Typhimurium-specific PNA targeting ftsZ resulted in elongated cells that were not observed in E. coli, providing phenotypic evidence of the selectivity of PNA-based antimicrobials. Analysis of the genomes of E. coli and S. Typhimurium gave a conservative estimate of >150 PNA targets that could potentially discriminate between these two closely related species. This work provides a basis for the development of a new class of antimicrobial with a tuneable spectrum of activity.Peer reviewedFinal Published versio

Evaluation of a hand-held far-ultraviolet radiation device for decontamination of Clostridium difficile and other healthcare-associated pathogens

<p>Abstract</p> <p>Background</p> <p>Environmental surfaces play an important role in transmission of healthcare-associated pathogens. There is a need for new disinfection methods that are effective against <it>Clostridium difficile</it> spores, but also safe and rapid. The Sterilray™ Disinfection Wand device is a hand-held room decontamination technology that utilizes far-ultraviolet radiation (185-230 nm) to kill pathogens.</p> <p>Methods</p> <p>We examined the efficacy of disinfection using the Sterilray device in the laboratory, in rooms of hospitalized patients, and on surfaces outside of patient rooms (i.e. keyboards and portable medical equipment). Cultures for <it>C. difficile</it>, methicillin-resistant <it>Staphylococcus aureus</it> (MRSA), and vancomycin-resistant <it>Enterococcus</it> (VRE) were collected from commonly-touched surfaces before and after use of the Sterilray device.</p> <p>Results</p> <p>On inoculated surfaces in the laboratory, application of the Sterilray device at a radiant dose of 100 mJ/cm² for ~ 5 seconds consistently reduced recovery of <it>C. difficile</it> spores by 4.4 CFU log₁₀, MRSA by 5.4 log₁₀CFU and of VRE by 6.9 log₁₀CFU. A >3 log₁₀ reduction of MRSA and VRE was achieved in ~2 seconds at a lower radiant dose, but killing of <it>C. difficile</it> spores was significantly reduced. On keyboards and portable medical equipment that were inoculated with <it>C. difficile</it> spores, application of the Sterilray device at a radiant dose of 100���mJ/cm² for ~ 5 seconds reduced contamination by 3.2 log₁₀CFU. However, the presence of organic material reduced the lethal effect of the far-UV radiation. In hospital rooms that were not pre-cleaned, disinfection with the Sterilray device significantly reduced the frequency of positive <it>C. difficile</it> and MRSA cultures (<it>P</it> =0.007).</p> <p>Conclusions</p> <p>The Sterilray™ Disinfection Wand is a novel environmental disinfection technology that rapidly kills <it>C. difficile</it> spores and other healthcare-associated pathogens on surfaces. However, the presence of organic matter reduces the efficacy of far-UV radiation, possibly explaining the more modest results observed on surfaces in hospital rooms that were not pre-cleaned.</p