Waterless agents for decontaminating the hands.
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Biomedical subjects
Publications and source records attributed to C W Stratton.
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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.
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.
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.
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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.
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.
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.
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.
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.
During a five year period, 28 episodes of spontaneous bacterial peritonitis were documented. The number of cases recognized annually increased during the study period. Clinical and laboratory features of spontaneous bacterial peritonitis were similar to those previously reported; however, mortality was considerably lower (57 per cent). Factors associated with adverse prognosis were increasing hepatic encephalopathy, more than 85 per cent granulocytes in peripheral blood or ascitic fluid, total bilirubin greater than 8 mg/dl and serum albumin less than 2.5 g/dl. Temperature greater than 38 degrees C was associated with increased survival. Infection by enteric organisms was associated with higher mortality than infection by nonenteric organisms. Unexpectedly, patients with bacteremia fared no worse than those whose blood remained sterile. The data suggest that in patients with leukocyte counts greater than 1,000 cells/mm3 and more than 85 per cent granulocytes in their ascitic fluid, the likelihood of spontaneous bacterial peritonitis is high. Such patients deserve empiric antibiotic therapy pending the results of appropriate cultures.
Mycobacterium szulgai, a scotochromogenic mycobacterium, is a newly recognized pathogen of man and has been reported to cause pulmonary infections, olecranon bursitis and cervical adenitis. We isolated M. szulfai from granulomatous tissue removed at surgery from a young florist with the carpal tunnel syndrome. The organism was susceptible to ethambutol and rifampin but resistant to isoniazid. Cure was achieved by debridement and chemotherapy with ethambutol and rifampin. Neither the source in our patient nor the natural habitat of M. szulgai is known. Because it resembles M. gordonae and M. flavescens, common scotochromogenic mycobacteria in tapwater, care must be taken to avoid dismissing M. szulgai as a contaminant when it is isolated from tissue.
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Through the use of time-kill kinetic studies, the bactericidal activity of cefotaxime (CTX) and desacetylcefotaxime (dCTX) alone and in combination against 18 strains of Bacteroides fragilis group was studied. Each isolate was tested at subinhibitory, inhibitory, and suprainhibitory concentrations of each drug as determined from the MIC values. Overall CTX was more bactericidal than dCTX at each of the three concentration levels tested. The combination of CTX and dCTX showed comparable bactericidal activity to CTX at the subinhibitory and inhibitory concentrations, even though each component was present at only one-half the concentration of CTX alone. At suprainhibitory concentrations, the combination of CTX/dCTX appeared synergistic since the combination with each component at a concentration of 1 x MIC was as bactericidal as CTX at a concentration of 4 x MIC. CTX and dCTX alone and in combination exhibited comparable bactericidal activity against test isolates with high (greater than or equal to 32 micrograms/ml) or low (less than or equal to 16 micrograms/ml) MICs. Thus, in vitro the combination of CTX and its naturally occurring metabolite dCTX interacts to produce an additive or synergistic effect against strains of B. fragilis group. Whether the in vitro testing of the combinations is more relevant to clinical outcome than testing CTX alone needs further study.
We evaluated cefotaxime (CTX) alone and in combination with its metabolite, desacetylcefotaxime (dCTX) against strains of Staphylococcus aureus that produce the four recognized variants of staphylococcal beta-lactamase and a beta-lactamase-producing isolate characterized by the expression of borderline resistance to methicillin. Although macrodilution MICs revealed that dCTX was less active than CTX against these strains (geometric means of 16 micrograms/ml and 4 micrograms/ml, respectively), the addition of clinically achievable concentrations of dCTX to CTX resulted in a reduction in the observed CTX MICs. This effect was similar to although less pronounced than that obtained by combining clavulanic acid with cefazolin. The increased antistaphylococcal activity noted by MIC determinations was confirmed with kill-kinetic studies. Determination of the relative rates of hydrolysis of selected cephalosporins showed that neither CTX nor dCTX were appreciably hydrolyzed by the variant staphylococcal enzymes. Evaluation of the effect of CTX and dCTX upon the staphylococcal beta-lactamases demonstrated that neither agent inhibited the destruction of a 100 microM solution of nitrocefin, although the reduction of CTX and cefazolin MICs by low concentrations of dCTX suggests that the dCTX metabolite may act as a competitive inhibitor of beta-lactamase. These observations may explain the previously demonstrated clinical efficacy of CTX used alone for the treatment of serious infections caused by S. aureus.
The bacterial activity of lomefloxacin and ciprofloxacin against selected pathogens was compared using kill-kinetic methods to assess inhibitory (1 x MIC) and suprainhibitory (4 x MIC) concentrations. Five strains each of the following microorganisms were studied: Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. We found that lomefloxacin was 8- to 16-fold less active than ciprofloxacin as measured by MICs. However, the bactericidal activities of both lomefloxacin and ciprofloxacin were comparable when concentrations 1 x MIC and 4 x MIC were tested. For many of the isolates tested, such concentrations would be achieved clinically. The low MICs seen for the Gram-negative bacilli did not correlate with killing ability for either drug: concentrations 8-16 x MIC were needed for 99.9% killing of the final inoculum. Although higher concentrations of lomefloxacin are needed for inhibitory and bactericidal activity, the improved pharmacokinetics of lomefloxacin may result in this agent being comparable to ciprofloxacin.
Nineteen strains of the Bacteroides fragilis group were used to determine the bactericidal activity of ceftizoxime, cefoxitin, cefotetan, and penicillin G with time-kill kinetics studies. Each antimicrobial agent was tested at subinhibitory (1/2 X MIC), inhibitory (1 X MIC), and suprainhibitory (4 X MIC) concentrations. Penicillin G exhibited virtually no sustained bactericidal activity at any of the antimicrobial concentrations tested. At subinhibitory concentrations, ceftizoxime was considerably more bactericidal than cefoxitin or cefotetan: At 12 hr, ceftizoxime killed 89% of the inoculum, whereas cefoxitin and cefotetan killed 35% and 33% of the inoculum, respectively. At inhibitory concentrations, ceftizoxime was again more bactericidal than cefoxitin and cefotetan: At 12 hr, ceftizoxime killed 90% of the inoculum, whereas cefoxitin and cefotetan killed 78% and 73%, respectively. At suprainhibitory concentrations, all three antimicrobial agents showed comparable bactericidal activity at 12 and 24 hr. Ceftizoxime and cefoxitin had somewhat lower killing rates overall against test strains with high MICs (greater than or equal to 32) versus low MICs (less than or equal to 16). However, at subinhibitory concentrations, ceftizoxime killed the B. fragilis group strains with high or low MIC values more effectively than cefotetan killed strains with low MICs. At the highest antibiotic concentrations tested (4 X MIC), only slight differences were seen in the bactericidal activity of the three compounds, regardless of MICs.