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Biomedical subjects

C W Stratton

Publications and source records attributed to C W Stratton.

At least 73 records · Page 4Linked to original sources

Bactericidal activity of deptomycin (LY146032) compared with those of ciprofloxacin, vancomycin, and ampicillin against enterococci as determined by kill-kinetic studies.

This study used kill-kinetic methods to provide data on the bactericidal activity of subinhibitory (1/2 X MIC), inhibitory (1 x MIC), and suprainhibitory (4X, 6X, and 8X MIC) concentrations of deptomycin (LY146032) against strains of enterococci compared with those of ciprofloxacin, vancomycin, and ampicillin. Deptomycin was the most active agent tested, as determined by broth microdilution methods, with all strains being inhibited at concentrations less than or equal to 2 micrograms/ml. The kill-kinetic demonstrated that deptomycin had greater activity at all concentrations tested than the other cell wall-active agents; regrowth was seen, however, at lower concentrations. At higher concentrations (6X and 8X MIC), all agents tested demonstrated the same or less bactericidal activity than at 4X MIC, presumably due to the Eagle effect. Nevertheless, these results suggest that further evaluation of deptomycin as a therapeutic agent for serious enterococcal infections is warranted.

Ampicillin

Activity of LY146032 compared with that of methicillin, cefazolin, cefamandole, cefuroxime, ciprofloxacin, and vancomycin against staphylococci as determined by kill-kinetic studies.

Kill-kinetic methods were used to provide data on the bactericidal activity of subinhibitory (0.5x MIC), inhibitory (1x MIC), and suprainhibitory (4x MIC) concentrations of LY146032 against methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis. These bactericidal activities were compared with those of methicillin, cefazolin, cefamandole, cefuroxime, ciprofloxacin, and vancomycin. LY146032 was among the most active of the antistaphylococcal agents tested, as determined by broth microdilution methods, with all strains being inhibited at concentrations of less than or equal to 1 microgram/ml. Time kill-kinetic studies demonstrated that at 4x MIC, LY146032 was rapidly bactericidal against all strains of staphylococci. Our data show that LY146032 has significant bactericidal activity against staphylococci in comparison with other antistaphylococcal agents. Further evaluation of LY146032 against serious staphylococcal infections is warranted.

Anti-Bacterial Agents

Comparison of kill-kinetic studies with agar and broth microdilution methods for determination of antimicrobial activity of selected agents against members of the Bacteroides fragilis group.

Kill-kinetic studies often are used to determine the rate and degree of killing of aerobic bacteria by antimicrobial agents. Few studies, however, make use of this method for determining antimicrobial activity against anaerobic bacteria. To evaluate kill-kinetic studies for anaerobes, kill-kinetic studies were performed for selected antimicrobial agents against members of the Bacteroides fragilis group and compared with MICs obtained by using a reference agar dilution method and a broth microdilution method. Results of the kill-kinetic studies showed that the degree of killing over a 24-h test period was related to the MIC for the test organism. In general, the higher the MIC of an antimicrobial agent for a test organism, the less the killing observed. In addition, these studies demonstrate subtle differences in bactericidal activity at various concentrations of the antimicrobial agents, which cannot be determined by agar or broth dilution methods. Kill-kinetic studies are a useful addition to dilution methods for the evaluation of antimicrobial agents against anaerobes.

Anti-Bacterial Agents

Controlled evaluation of modified radiometric blood culture medium supplemented with gelatin for detection of bacteremia and fungemia.

Although the addition of 1.2% gelatin to broth blood culture media containing sodium polyanetholesulfonate has been shown to enhance detection of certain bacteria, including Neisseria meningitidis, N. gonorrhoeae, Peptostreptococcus anaerobius, and Gardnerella vaginalis, the effect of such supplementation on the detection of other microorganisms causing bacteremia and fungemia is not known. Therefore, we studied BACTEC 6B medium with and without gelatin in 6,833 paired comparisons to examine the effects of supplementation on both the yield and the speed of detection of sepsis. More aerobic and facultative bacteria grew in the 6B than in the 6B-gelatin medium (P less than 0.001), especially staphylococci (P less than 0.01), Escherichia coli (P less than 0.01), other members of the family Enterobacteriaceae (P less than 0.05), and Acinetobacter spp. (P less than 0.05). When microorganisms grew in both bottles, they did so earlier in 6B than in 6B-gelatin (P less than 0.001). We conclude that the 6B medium in its present formulation is superior to 6B medium supplemented with 1.2% gelatin.

Bacteria

Rapid diagnosis of Candida sepsis in surgical patients.

Systemic candidiasis, an increasingly common disease, is associated with an extremely high mortality. Because of toxicity associated with amphotericin B therapy, clinicians are reluctant to initiate therapy until the presence of candidiasis is conclusively demonstrated. Using culture methods, such proof may not be forthcoming or may be available only late in the course of the disease. During the last 17 months, a new antigen latex agglutination test for candidiasis has been evaluated. Results indicate that this new test allows early, accurate diagnosis of the disease. In 36 consecutive cases of culture-proven candidiasis in surgical patients, the test was found to be 94.4 per cent sensitive and 100 per cent specific. On the basis of these findings initiation of amphotericin B therapy in patients with a positive Candida antigen titer is recommended.

Adult

Effect of clavulanic acid on the activity of ticarcillin against Pseudomonas aeruginosa.

We studied the ability of clavulanic acid (CA) to induce beta-lactamase in Pseudomonas aeruginosa isolates and what effect this might have on the susceptibilities to beta-lactam agents. We first used a disk approximation method to test 4 laboratory and 16 clinical P. aeruginosa isolates against antipseudomonal beta-lactam agents for truncation by CA and found this to be very common. All antimicrobial compounds except imipenem demonstrated truncation in the vicinity of CA. We also evaluated the extent to which chromosomal beta-lactamase is induced by CA and found this to occur to some degree in most isolates and to be dependent on the concentration of CA. Finally, we performed time kill curves on these isolates to compare bacterial growth in ticarcillin alone with growth in ticarcillin-CA (the CA at 2 or 4 micrograms/ml). We found that CA at this concentration has neither an antagonistic nor a synergistic antibacterial effect in combination with ticarcillin.

Anti-Bacterial Agents

Controlled evaluation of the agar-slide and radiometric blood culture systems for the detection of bacteremia and fungemia.

A commercially available agar-slide blood culture bottle (Septi-Chek; Roche Diagnostics, Div. Hoffman-La Roche, Inc., Nutley, N.J.) was compared with the radiometric blood culture system (BACTEC; Johnston Laboratories, Inc., Towson, Md.) in 8,544 paired blood cultures from adult patients. The systems were inoculated with equal volumes (10 ml) of blood. Overall, there was no statistically significant difference between the two systems in the recovery of clinically important microorganisms, but significantly more members of the family Enterobacteriaceae other than Escherichia coli were detected by the agar-slide system (P less than 0.005). The agar-slide system detected more fungi, and the BACTEC detected more anaerobic bacteria; however, small numbers of recovered organisms precluded statistical significance. When microorganisms grew in both systems, their presence was detected one or more days earlier in the BACTEC (P less than 0.001). More contaminants grew in the agar-slide system (P less than 0.001). Both systems performed well, and either system should provide high yield and prompt detection of positive blood cultures in patients with bacteremia and fungemia if used in an optimal way as recommended by the respective manufacturers.

Bacteria

Evaluation of spot CAMP test for identification of group B streptococci.

The CAMP (Christie-Atkins-Munch-Petersen) test is commonly used for the presumptive identification of Streptococcus agalactiae (Lancefield group B). Using 350 clinical isolates of beta-hemolytic streptococci, we compared a 30-min spot CAMP test with the standard overnight CAMP test and the Lancefield precipitin test. We found 99% agreement among all three tests for all streptococci tested. The spot CAMP test is a rapid, inexpensive, and accurate method for identifying group B streptococci.

Bacteriological Techniques

Multicenter collaborative evaluation of a standardized serum bactericidal test as a prognostic indicator in infective endocarditis.

One hundred twenty-nine patients with bacterial endocarditis were evaluated in a multicenter collaborative study to determine whether a standardized serum bactericidal test could predict the outcome of the infection. All centers used a microdilution test method that defined all known test variables, including inoculum size, culture medium, dilution technique, incubation time, method of subculture, and bactericidal endpoint. Peak serum bactericidal titers of 1:64 or more and trough serum bactericidal titers of 1:32 or more predicted bacteriologic cure in all patients. The traditionally recommended serum bactericidal titer of 1:8 had statistically significant predictive accuracy at trough antibiotic levels only. The serum bactericidal test was a poor predictor of bacteriologic failure and ultimate clinical outcome, which depends on many factors. Wider recognition by physicians and clinical microbiologists that this in vitro test of antimicrobial activity can accurately predict bacteriologic success but cannot accurately predict either bacteriologic failure or clinical outcome could lead to a better consensus about its appropriate use. On the basis of the results of this study, peak serum bactericidal titers of 1:64 or more and trough serum bactericidal titers of 1:32 or more are recommended to provide optimal medical therapy for infective endocarditis.

Adolescent

Falsely elevated serum creatinine levels secondary to the presence of 5-fluorocytosine.

The Kodak Ektachem (Eastman Kodak Co., Rochester, NY) is a new clinical chemistry analyzer that uses an enzymatic method to measure creatinine. The authors report the case of a patient with falsely elevated creatinine levels that were caused by the presence of 5-fluorocytosine. A review of the literature confirmed that this can occur, but well documented reports are not found. In order to determine the magnitude of this interference, the authors plotted creatinine levels versus 5-FC concentration. Significant interference is seen with therapeutic levels of 5-FC. Both clinicians and pathologists should be aware of this phenomenon.

Aged

Imipenem-induced resistance to antipseudomonal beta-lactams in Pseudomonas aeruginosa.

Using clinical isolates of Pseudomonas aeruginosa, we studied the ability of imipenem to antagonize the activity of nine other antipseudomonal beta-lactam antimicrobial agents. Imipenem caused truncation of the zones of inhibition in a disk diffusion test for 91 to 100% of the strains, depending on the beta-lactam tested. Addition of subinhibitory concentrations of imipenem caused a fourfold or greater increase in MICs for 72 of 74 isolates and in 20 to 87% of the tests, again depending on the antibiotic tested. beta-Lactamase assays with both whole-cell suspensions and cell sonicates showed that exposure to subinhibitory concentrations of imipenem resulted in a beta-lactamase production supported the hypothesis that induction of beta-lactamase was responsible for antagonism. In hydrolysis studies with a beta-lactamase extract, most of the antagonized drugs were either not hydrolyzed or only poorly hydrolyzed. We conclude that imipenem induces significantly elevated levels of beta-lactamase in P. aeruginosa. This increase in beta-lactamase is associated with increased resistance of the organism to many other beta-lactam agents.

Anti-Bacterial Agents

Comparison of the effect of refrigerated versus room temperature media on the isolation of Neisseria gonorrhoeae from genital specimens.

We evaluated the effect of medium temperature at the time of inoculation on the isolation of Neisseria gonorrhoeae from urethral and cervical swabs. There were no major differences in the isolation rates of 176 positive cultures on cold or warm media. Colonies tended to be larger and more numerous on room temperature plates after 24 h; however, colonies on most refrigerated plates were easily recognized at 24 h, and growth was essentially the same on both plates after 48 h.

Cervix Uteri

Thermonuclease test for same-day identification of Staphylococcus aureus in blood cultures.

We used a thermonuclease test to presumptively identify Staphylococcus aureus directly in blood cultures on the same day that a smear of the broth showed gram-positive cocci in clusters. There were no discrepancies between the identification of S. aureus directly from 250 blood cultures and identification by the tube coagulase test which was performed on the 18- to 24-h subculture isolates. These rapid results were clinically relevant and enabled physicians to make more timely and cost-effective decisions about antibiotic therapy.

Humans