Maintain the vacuum for an additional 2 to 3 minutes and then remove; purchased May Unbuffered, low-opacity, long-fiber tissue. No recycled or wooden fibers. No optical brighteners. Adhesive: potato starch, pH 7. Teflon PTFE film, pliable, chemically inert, nontoxic, and non-adsorbent; 3 mil thick, 10 in wide, ft roll; Lot number C; A head diameter: Rectangular profile silicone gasket with pressure-sensitive adhesive; low density, low compression set, fire retardant silicone foam - White - Cut, release paper removed.
Copper: ok - Silver: ok; localized white spot - Lead: thick white and yellow compact corrosion; with fluffy spots. Medium density fiberboard panel coated in Dacrylate Clear Acrylic Emulsion varnish 2-butoxyethanol - Brown, Transparent - Cut into small blocks using bandsaw - cut edges are uncoated.
Corrugated polypropylene board; May ; 4 mm thickness. Purchased in May Reference Oddy Adhesive: Potato starch, pH 7. Paper faced foamboard. Acquired in Extrusion details unknown. Heat Sealable barrier film; Details: heat sealable barrier film silver on outside, grey inside.
Heat Sealable Barrier film; Details: metalized barrier film, silver with red lettering on outside, grey on inside: Oriented Polypropylene 0. Barrier film; Details: heat sealable barrier film, silver with writing on outside and grey on inside: biaxially oriented nylon 0.
Barrier film; Details: heavy duty heat sealable barrier film. Barrier film; Details: super heavy duty heat sealable barrier film. Copper: slight reddening, yellowing, or rainbow-like color change; Formation of up to 20 black spots Temporary Silver: similar to control; slight yellowing, purpling, or darkening. Temporary Lead: darkening; spots of corrosion where in direct contact with sample material Temporary.
Copper: slight reddening, yellowing, or rainbow-like color change Temporary Silver: slight yellowing, purpling, or darkening. Temporary Lead: significant darkening and purple, red, green discoloration; white fluffy crystal formation; coupon eaten away where in direct contact with sample material.
Copper: slight reddening, yellowing, or rainbow-like color change; Formation of up to 20 black spots Temporary Silver: Coupons look similar to the controls. Copper: Inconsistent;reddening, yellowing, or darkening Fail Silver: slight yellowing, purpling, or darkening.
Temporary Lead: heavy, overall white fluffy crystal formation; coupon eaten away where in contact with sample material Fail. Copper: severe blackening Fail Silver: slight yellowing, purpling, or darkening. Copper: severe blackening; more alteration where in contact with sample material Fail Silver: slight yellowing, purpling, or darkening. Drywall joint compound: premixed with water, 4. Contains 1. Received Spring Unknown purchase date.
Fibers heat treated with ProTex r fluorochemical anti-soiling treatment. Cork roll with self-adhesive; natural lignocellulosic plant material, unknown adhesive; Purchased: Natural cork roll no adhesive ; 2mm thickness x 2. Transparent Pro-form formed plastic; thickness: 0. Pro-form formable plastic; Ethyl vinyl acetate; thickness: 0.
Emulsion varnish; cured 2 weeks before testing; batch ; date of manufacture: March 16, Expanded polyethylene foam; produced as bun; Chemical Components: polyethylene. Foamed round gasket; expanded white silicone tubular gasket. Volara type A foam; white; 4 pcf density; 0. Use on micro-fiber cloth to clean surface of glazing. However, their extruded silicone is a different compound and should not be confused with their sheeting; purchased August However, their extruded silicone is a different compound and should not be confused with the sheeting; purchased August Aluminum honeycomb; Chemical Components: 0.
Polypropylene corrugated board; Non-archival. Extruded twin wall fluted plastic sheet. White trapezoidal backer rod foam, Top: 1. Anti-reflective, abrasion resistant, and anti-static, 3mm acrylic sheet. Printable magnetic sheet with white matte thermoplastic binder on one side often used for retail graphics ; flexible in nature; thickness: 0. Printable magnetic sheet with white glossy thermoplastic binder surface on one side; thickness: 0. AIN Plastics. CR Laurence. Tested without red adhesive liner.
Volara A WH closed cell foam. Polystone G polyethylene board. Komacel Plus, striated PVC board. Striated; PVC board. Soloman Scientific. Paper weight: 10 gsm, 60 microns thick;. Netherland Rubber Company. Netherland Rubber Co. Sealed Air Plant in Kentucky. Canal Rubber Supply Co. Aluminum is fused and melted using a laser from a bed of metallic powder. This process fully melts the powder rather than just sintering it, creating a solid, homogenous aluminum alloy; note: sample jars contained less than 2g of sample.
Rogers Corporation. White silicone foam with pressure sensitive adhesive on one side; purchased januray Huntsman Chemical. Freeman Manufacturing and Supply Co. Clear silicone rubber sheet; durometer: 40; manufacturer may dyeCut this sheeting if drawings are supplied.
Their extruded silicone can be a different compound than the tested sheeting. Intramedic non-radiopaque polyethylene tubing, model Colored one component silicone sealant ; cured 24 hours. Polymer - adhesive - caulk or sealant.
Ultralon Foam Group. Polyethylene foam board; 34mm thick, 2ft x 3ft. Produced in Ho chi minh, Vietnam - only manufacture site for Ultralon. Batch made with pellets sourced from Germany. Can laminate with heat or glue. Polyethylene foam board; 41mm thick, 2ft x 3 ft.
Polyethylene foam board; Details: Testing as possible customizable 'foam' or cushioning structure for shipping art. Rainbow Rubber. Lead and copper coupons slightly changed: small specks of white corrosion products on lead with uneven patina, and slight discolouration of copper. Compression Seal, permanent elastic silicone , Clear. Foam PVC. Slight tarnish on silver coupon, moderate corrosion on lead coupon.
Tarnishing on copper coupon in keeping with control copper coupon. Brush seal, panel connection system, permanent elastic silicone , Clear. In vitrine or case. Suitable for permanent use to apply to leading edges of doors and opposing edges. Benchmark Sueded polyethylene with adhesive , Black.
Benchmark Sueded polyethylene with adhesive , Grey. HMPE High molecular weight polyethylene? Polypropylene , white. The tests all exploded stopper blew off during testing, so results may not be accurate. Only slight reaction with lead, so could probably be used for permanent storage so long as not direct contact with metal, and well ventilated.
Some contaminaton of the coupons, but most tests had better results than the controls, and none were worse than the controls. The duplicate nature of the tests allowed contamination to be distingished. Some change in the lead, but the yellow coating appeared on the control too, so I suspect it is contamination on the stoppers.
Some contamination of the coupons, but most tests had better results than the controls, and none were worse than the controls. The duplicate nature of the tests allowed contamination to be distinguished. Pb and Ag unchanged, Cu coupon changed colour. Suitable for temporary use or permanent use with selected collections only. In order to make accurate predictions about treatment outcome, laboratories must not only have a reproducible and reliable method, but the in vitro data generated by these methods must have relevance to the physiologic conditions found within a patient.
The benefit of this susceptibility testing system is that it is a simple and robust method enabling extraordinary degrees of reproducibility, despite being performed by a wide variety of laboratories. However, the greatest strength of this method may also be its greatest weakness.
Because this method is so exceedingly simple, it fails to account for factors that are undoubtedly critical for accurate prediction of treatment outcome. For example, current susceptibility methods do not take into account factors such as patient immune system function, site of infection with a few exceptions , and drug-drug interactions. It is perhaps not surprising that some have found significant limitations in the ability of these methods to predict outcome.
Interestingly, this finding was not specific to any one antimicrobial, organism, or site of infection. There are many possible explanations for the rule, one of which is that our methods fail to account for situations in which a patient is receiving more than one antimicrobial.
Traditional susceptibility testing relies on the assessment of individual organism-antimicrobial combinations from which some objective measure of antimicrobial activity is derived. What is not considered is how those organisms will respond to therapy when more than one antimicrobial is used. Our routine susceptibility testing methods fail to account for these dynamic treatment situations.
Given the frequency with which combination therapy is employed, a method capable of assessing antimicrobial interaction and activity could be of some value. Synergy testing is done with sophisticated susceptibility testing techniques that account for combinations of antimicrobials and measure their cumulative efficacy. What follows is a detailed discussion of the methods that exist for assessing antimicrobial synergy.
Specifically, the technical aspects of performing synergy testing will be described, as well as the interpretation of the data provided. The review will then discuss the clinical scenario in which synergy testing has most commonly been applied: testing of pathogens isolated from cystic fibrosis CF cases.
The majority of this discussion will focus on in vitro data, and where available, outcome studies will be considered. Regrettably though, very few outcome data are available to support the use of synergy testing to predict which antimicrobial combinations will be most effective. What outcome data are available suggest that synergy testing is no better than conventional testing with respect to predicting patient outcome.
In some cases, the literature suggests that it is in fact deleterious to patient care. Of note, a plethora of antimicrobial combinations not in current use have been assessed for synergy. Many of these combinations have not been used for patient care and are therefore outside the scope of this minireview. In addition, the subject of enterococci and high-level aminoglycoside resistance testing will not be discussed. These tests have been shown to predict the presence or absence of synergy but are themselves not synergy tests.
The goal of synergy testing is to assess the in vitro interaction of antimicrobial combinations to determine whether the effect of the two antimicrobials is greater than the sum of their individual activities. Antimicrobial combinations can act additively, where the cumulative antimicrobial effect is simply the sum total of the two antimicrobials acting together, or they can act synergistically, where the combined activity is greater than the sum of their activities when used individually.
Conversely, these methods are also capable of identifying combinations that are antagonistic. There are four primary methods by which synergy can be assessed in vitro : the checkerboard method, multiple-combination bactericidal antimicrobial testing MCBT , Etest, and time-kill curve assays. The checkerboard method assesses the activities of antimicrobial combinations tested at clinically achievable concentrations in serial 2-fold dilutions.
The assay combinations are generally designed to include antimicrobials from different classes. The data produced by the checkerboard assay are analyzed in terms of the fractional inhibitory concentration index FIC Fig. FICs in the 0. The limitations of this method are that it only tests antimicrobials for a fixed incubation time, it can require a large number of reagents and resources to test different antimicrobial combinations, and it is not capable of testing more than two antimicrobials at a time.
In other words, combinations of three and four antimicrobial cannot be tested. The multiple-combination bactericidal test is designed to test combinations of two, three, or four antimicrobials simultaneously and is based on the premise of doing so at pharmacologically allowable blood concentrations. The concentration used in each experiment is defined by what can be achieved in a patient's serum.
In contrast to checkerboard synergy testing methods, only fixed concentrations are assessed with MCBT. The primary variable tested is the combination of the antimicrobial tested. These experiments are typically carried out in a series of well microtiter plates that contain the desired antimicrobial combinations and concentrations. At 24 and 48 h, the wells are inspected for turbidity, and wells without visual evidence of growth are subcultured to solid medium and assessed after overnight incubation for MBC testing establishes the concentration of antimicrobial that is necessary to kill This is also the fundamental principle used in MCBT, and its utility is limited because it relies on a somewhat arbitrary Furthermore, some have questioned the utility of MCBTs because of the highly technical nature of the testing and the difficulty in controlling variables 8.
TKAs take the principle of the MCBT, but rather than assessing cidal activity at a single point in time, the activity is assessed in a chronological fashion over a h incubation period. In contrast to the checkerboard assay, which assesses killing at a fixed time point and establishes the optimal concentration for killing, TKAs determine the rate of killing, which may be a more relevant metric to predicting patient outcome 9.
Within that document, a standardized protocol for time-kill assays is provided The inoculum is then incubated for a total of 48 h, with periodic 0. These samplings generally occur at 4, 8, 10, 12, and 24 h. The time-kill colony counts are then graphically represented as a function of time. Interpretation of TKAs can be difficult due to bacterial regrowth at later time points, and they are best assessed in the first 12 h.
Conventional, single-drug testing with the Etest otherwise known as gradient diffusion relies on the diffusion of a continuous concentration gradient of antimicrobial from an impregnated strip into solid agar. Etest strips are placed on agar medium that has been inoculated with a lawn of the test organism. The Etest is then incubated overnight, and the point at which the elliptical no-growth zone touches the strips can be read as the MIC.
There are two modifications of this procedure which have been developed to assess synergy. In the first method, two Etest strips, each containing one of the antimicrobials of interest, are placed perpendicular to each other, intersecting at the MIC for each antimicrobial when tested alone. As with the checkerboard technique, the interpretation of Etest synergy is based on the FIC calculation, which is presented in Fig.
A second approach to Etest synergy places the first Etest strip containing drug number 1 on the agar which has been inoculated with a lawn of the test organism. The Etest is allowed to sit for 60 min and is then removed. A second strip containing drug number 2 is then placed in the same position. This represents the synergy portion of the assay.
Control Etests for each individual drug are placed on the same plate such that they do not interfere with the synergy test. With four different approaches to synergy testing, a number of studies have endeavored to compare their results in an effort to identify the best method.
One challenge in doing so is that there is no true gold standard for synergy, so it is difficult to know which results are correct. Nonetheless, Lewis and colleagues were able to conclude that the checkerboard method was inferior to Etest and TKAs when assessing antifungal synergy for Candida species This finding may be due to the MIC clustering that broth microdilution can demonstrate in antifungal testing.
This phenomenon may make it difficult to discriminate between susceptible and intermediate isolates and, therefore, hinder the performance of checkerboard testing. For bacterial testing, White and colleagues compared the TKA, checkerboard, and Etest methodologies for Escherichia coli , Enterobacter cloacae , Pseudomonas aeruginosa , and Staphylococcus aureus. The authors conclude that this is a positive finding and, given, the relative simplicity of the Etest method, suggest that it could be a viable alternative to TKA and checkerboard testing.
However, if we accept that TKA is the gold standard for assessing synergy, then it is difficult to see the Etest as an acceptable method in the clinical laboratory with up to one quarter of results being discrepant and potentially erroneous. Several other studies have evaluated the comparability of synergy testing and found various degrees of agreement. Cappelletty and Rybak compared checkerboard to TKA for Pseudomonas aeruginosa and found almost no correlation between the two methods.
Their primary finding was that TKA demonstrated consistent synergism at various concentrations of antimicrobial, while checkerboard testing could only demonstrate indifference These two studies reflect the consensus of others who have compared synergy methods for different antimicrobial combinations and bacterial species and all found the same thing, that no two synergy methods produce comparable results 14 , — As was just discussed, the literature suggests that no two synergy methods produce comparable results.
It is therefore unlikely that, as a whole, synergy testing will prove to be clinically relevant. However, it is possible that one of these methods produces results that correlate with patient outcomes. As was stated earlier, there is no true gold standard for synergy testing. TKA appears to be the primary comparator most commonly used in the literature, which is likely due to the fact that NCCLS standardized the method. This makes some sense, as the method produces dynamic information about organism killing over time, something not provided by other methods.
However, only a few studies have attempted to establish the true clinical relevance of synergy testing through outcome-based studies, and none of these evaluate TKA. The result is that a tremendous amount of in vitro data analyzing synergistic antimicrobial combinations are available, but almost none of that information can be linked to treatment outcomes.
Despite the paucity of outcome data, synergy testing has been used to predict patient outcomes in cystic fibrosis patients. The following sections will review what is known about the synergy testing in this patient population and discuss the applicable outcome studies. Cystic fibrosis CF patients may be at greater risk for developing multidrug-resistant infections than any other patient population Organisms such as Pseudomonas aeruginosa , Burkholderia cepacia , and Stenotrophomonas maltophilia are common pathogens in these patients and are often extremely resistant, leaving few or no therapeutic options.
Initially, cystic fibrosis patients seemed like ideal candidates for synergy testing. Indeed, until , the Cystic Fibrosis Foundation had recommended that synergy testing be considered in CF patients with multidrug-resistant organisms. The CF Referral Center at Columbia University was established in to satisfy the growing demand for synergy testing 6. The literature shows that all of the four methods discussed above have been applied to cystic fibrosis isolates.
However, the two methods most commonly used have been the checkerboard method and the MCBT method. Taken together, it is difficult to make any general conclusions from this body of literature, though perhaps the disparity of findings is by its nature informative. It is clear that broad statements about synergistic combinations for specific organisms cannot be made.
If synergy testing is to be useful clinically, patient isolates would require testing on a case-by-case basis. The literature has primarily focused on multidrug-resistant organisms and has come to a variety of conclusions. After evaluating an average of
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