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Biomedical subjects

C W Stratton

Publications and source records attributed to C W Stratton.

At least 19 recordsLinked to original sources

Blastomycosis in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To describe the clinical, demographic, radiographic, diagnostic, and therapeutic aspects of blastomycosis in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A retrospective survey. SETTING: Ten university medical centers and community hospitals, six in geographic areas endemic for Blastomyces dermatitidis, and four outside the endemic area. PATIENTS: We identified 15 patients with blastomycosis and positive serologic test results for human immunodeficiency virus (HIV). MEASUREMENTS: A diagnosis of blastomycosis was based on a positive culture (14 patients) or typical histopathologic features (one patient) for B. dermatitidis in clinical specimens. RESULTS: Twelve of 15 patients had a previous or concomitant AIDS-defining illness at the time of diagnosis of blastomycosis, and only one patient had a CD4 lymphocyte count of greater than 200 cells/mm3. Two patterns of disease emerged: localized pulmonary involvement (seven patients), and disseminated or extrapulmonary blastomycosis (eight patients). Central nervous system involvement was common (40%). Six patients died within 21 days of presentation with blastomycosis, including four patients with disseminated and two with fulminant pulmonary disease. Among the nine patients who survived longer than 1 month, all received amphotericin B as initial antifungal therapy, and most received subsequent therapy with ketoconazole. Only two of these nine patients died with evidence of progressive blastomycosis. CONCLUSIONS: Blastomycosis is a late and frequently fatal infectious complication in a few patients with AIDS. In these patients, overwhelming disseminated disease including involvement of the central nervous system is common, and it is associated with a high early mortality. Initial therapy with amphotericin B is appropriate in patients with AIDS and presumptive blastomycosis.

Acquired Immunodeficiency Syndrome

Characterization of four beta-lactamases produced by Staphylococcus aureus.

Staphylococcus aureus produces four types of beta-lactamase (A, B, C, and D). To investigate the effect of specific beta-lactamase type upon staphylococcal resistance, each beta-lactamase was purified to homogeneity, and the Michaelis constants (Km values) and turnover numbers (kcat values) for various penicillin and cephalosporin substrates were determined. Whereas Km values of the four beta-lactamases were comparable for penicillin G, cephalothin, and cefamandole, the type A and D enzymes exhibited greater affinity than the type B and C beta-lactamases for nitrocefin, cefazolin, and cephapirin. Conversely, the type B and C beta-lactamases exhibited greater kcat values than the type A and D enzymes against most of the cephalosporin agents, excluding nitrocefin. In contrast to earlier reports suggesting that the type B beta-lactamase is relatively inefficient in hydrolyzing penicillin G, we found only minor differences in the specific activities and kcat values of the type A, B, and C beta-lactamases. The type D beta-lactamase was distinctly less active against penicillin G, however, exhibiting only 15 to 25% of the kcat values of the other beta-lactamases. More than a 2,000-fold difference between the relative efficiencies of hydrolysis (kcat/Km) of cefazolin and cefuroxime by the type A beta-lactamase exists. This greatly exceeds the 60-fold difference in the stability of penicillin G and cefazolin with the same enzyme. Whereas the isoelectric points of the type A, B, and C beta-lactamases were similar, the value for the type D beta-lactamase was distinguishably lower (10.1 for types A, B, and C and 9.7 for type D). We conclude that marked differences in the stability of commonly used beta-lactams to hydrolysis by the staphylococcal beta-lactamases are present. This heterogeneity and the clinical implication thereof need to be considered in the antibiotic management of staphylococcal infection.

Cephalosporins

Controlled evaluation of BACTEC PLUS 27 and Roche Septi-Chek anaerobic blood culture bottles.

Becton Dickinson Diagnostic Instrument Systems (Sparks, Md.) recently introduced BACTEC high-volume aerobic and anaerobic bottles that accept up to 10 ml of blood for use on their nonradiometric blood culture instruments. Both bottles contain 25 ml of tryptic soy broth, 0.05% sodium polyanetholesulfonate, and mixed resins. We compared the anaerobic bottle, designated BACTEC PLUS 27 (BP27), with the Roche Septi-Chek (RSC) Columbia broth anaerobic bottle in a collaborative evaluation at three university hospitals. A total of 5,152 adequately filled blood cultures were obtained from adult patients with suspected bacteremia or fungemia. Staphylococcus aureus was recovered significantly more often (P less than 0.03) from BP27 bottles alone; there were no other significant differences in yield. When microorganisms were recovered from both anaerobic bottles, growth was detected earlier in BP27 than it was in RSC (P less than 0.001), especially for S. aureus (P less than 0.001) and Staphylococcus epidermidis (P less than 0.02). We conclude that the yield from BP27 bottles is equivalent to or better (S. aureus) than that from RSC anaerobic bottles with Columbia broth and that speed of detection is superior with BP27 bottles.

Adult

Focused microbiologic surveillance by specific hospital unit as a sensitive means of defining antimicrobial resistance problems.

An annual summary of susceptibility patterns for the predominant clinical isolates from hospitalized patients can be of considerable assistance in selecting antimicrobial agents for sepsis of unclear etiology, as well as for guiding empiric therapy for other serious infections. Yearly summaries of the susceptibility patterns of the predominant clinical isolates from all patients hospitalized at Vanderbilt University Hospital (VUH) from July 1987 through June 1991 revealed only minor differences over time in susceptibility patterns. However, the clinical impression of physicians treating patients in various intensive care units (ICUs) was that there were serious resistance problems in some units. To better define the prevalence of clinical isolates and their susceptibility patterns for patients within ICUs at VUH, we utilized a "focused microbiologic surveillance" technique that addressed each unit separately. Both the predominant clinical isolates and their susceptibility patterns were determined and compared with those from the hospital as a whole. Because susceptibility patterns of clinical isolates by site of infection within these units were considered important, we also reviewed the summaries of susceptibility patterns for blood, sputum, and urine isolates from patients in ICUs and compared these with the summaries from each ICU and from the hospital. No major resistance problems were identified on a hospital-wide basis. In contrast, focused microbiologic surveillance by specific hospital ICU revealed important differences in the prevalence of pathogens among units and at different times. In 1987, Pseudomonas aeruginosa was the single most common Gram-negative organism isolated in the neonatal unit, while Acinetobacter spp. were rarely isolated. By 1991, this trend was completely reversed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Bactericidal activity of ceftizoxime, cefotetan, and clindamycin against cefoxitin-resistant strains of the Bacteroides fragilis group.

The bactericidal activity of ceftizoxime, cefotetan, and clindamycin at 0.5 x MIC, 1 x MIC, and 4 x MIC was determined by killing kinetic studies for 12 cefoxitin-resistant strains of the Bacteroides fragilis group. Ceftizoxime and clindamycin had greater bactericidal activity than cefotetan. The degree of bactericidal activity of each compound increased as the concentration increased from subinhibitory (0.5 x MIC) to suprainhibitory concentrations (4 x MIC). Comparison of the bactericidal activity at the MIC of the test agents with the MIC showed greater killing of susceptible strains than the resistant strains. Interestingly, ceftizoxime was more active than clindamycin, or cefotetan, against strains with high cefoxitin MIC values.

Bacteroides fragilis

Controlled evaluation of BACTEC Plus 26 and Roche Septi-Chek aerobic blood culture bottles.

Blood culture bottles that accept up to 10 ml of blood have recently been introduced for the BACTEC nonradiometric blood culture system. The new formulation, designated BACTEC Plus, contains 25 ml of tryptic soy broth, 0.05% sodium polyanetholesulfonate, and mixed resins. In a collaborative study conducted at three university hospitals, we evaluated the BACTEC Plus 26 (BP26) aerobic bottle and the Roche Septi-Chek aerobic bottle with its agar slide paddle in 5,293 paired blood cultures. Significantly more microorganisms (P less than 0.001), especially Staphylococcus aureus (P less than 0.001), Staphylococcus epidermidis (P less than 0.01), enterococci (P less than 0.005), and members of the family Enterobacteriaceae (P less than 0.005), were detected by the BP26 bottle. When both bottles detected growth, BP26 did so earlier (P less than 0.001). In particular, S. epidermidis (P less than 0.001), streptococci (P less than 0.005), enterococci (P less than 0.05), and members of the family Enterobacteriaceae (P less than 0.001) were detected earlier by the BP26 bottle. We conclude that the BP26 bottle provides a yield and speed of detection of microorganisms superior to those of the Roche Septi-Chek aerobic blood culture bottle.

Adult

Use of extracts versus whole-cell bacterial suspensions in the identification of Staphylococcus aureus beta-lactamase variants.

We previously have shown that extracts of S. aureus isolates which produce the recognized serotypes of staphylococcal beta-lactamase (A, B, C, D) differ in the rates at which they hydrolyze selected cephalosporins, exhibiting substrate profiles which are distinctive for each serotype. In an effort to simplify the methods employed in identifying the different staphylococcal beta-lactamases, we evaluated whether distinctive substrate profiles could be obtained by using whole-cell suspensions of 115 beta-lactamase-producing isolates of S. aureus. Compared with extracts from the same strains, the whole-cell bacterial suspensions not only were simpler to prepare but enabled beta-lactamase typing of a higher proportion of the evaluated strains (86 versus 97%, respectively). Furthermore, the use of whole-cell bacterial suspensions enabled the simultaneous quantitation of the beta-lactamase activity exhibited by each strain. Additionally, by comparing the quantitative activity of beta-lactamase-induced and -uninduced preparations of the same strain, induction ratios (i.e., induced/uninduced activity) could be derived, yielding information regarding the regulation of beta-lactamase production by each strain. We believe that the utilization of whole-cell methods, such as those employed in this study, will facilitate the investigation of qualitative and quantitative differences in beta-lactamase production among clinical and reference isolates of S. aureus.

Cell-Free System

Characterization of mechanisms of resistance to beta-lactam antibiotics in methicillin-resistant strains of Staphylococcus saprophyticus.

The resistance mechanisms of methicillin-resistant strains of Staphylococcus saprophyticus were characterized. Penicillin-binding protein (PBP) studies demonstrated an inducible PBP identical to PBP 2a in the membranes of these isolates. The amount of beta-lactamase produced was minimal. PBP 2a is responsible for the methicillin resistance observed in these strains of S. saprophyticus.

Anti-Bacterial Agents

Comparative evaluation of radiometric tryptic soy broth versus radiometric tryptic soy broth with 10% sucrose for detection of bacteremia and fungemia in pediatric patients.

We compared BACTEC radiometric blood culture media with (8B) and without (6B) 10% sucrose for the detection of bacteremia and fungemia in pediatric patients at four university teaching hospitals that used identical methods for obtaining and processing specimens. Overall, the yields of microorganisms from 5,714 blood culture sets were no different in the two media, although a trend was noted favoring 6B for the detection of pneumococci. Speed of detection of positive results was faster in the 6B than in the 8B medium (P less than 0.05), largely due to the faster detection of Staphylococcus aureus in the 6B medium. We conclude that, overall, with pediatric patients the hypertonic 8B radiometric medium has no advantage and that it possibly has a modest disadvantage, compared with isotonic 6B radiometric medium.

Bacteria

Sensitivity, specificity, and predictive value of body surface cultures in a neonatal intensive care unit.

We analyzed 24,584 cultures obtained from 3371 infants during a three-year period to determine how frequently body surface culture isolates matched those obtained subsequently from body fluids. The sensitivity, specificity, and predictive values of surface cultures were calculated daily for the two weeks up to and including the day that a body fluid culture was obtained. Isolates from cultures of material from the ear canal, nasopharynx, axilla, umbilicus, groin, rectum, stomach, and endotracheal tube were rarely the same as those recovered from blood or fluids of the cerebrospinal, joint, pleural, pericardial, and peritoneal spaces. With a frequency of sepsis of 3.3% among patients in our neonatal intensive care unit, the optimum sensitivity, specificity, and positive predictive values of surface cultures were 56%, 82%, and 7.5%, respectively. These values did not improve substantially for any specific times of surface cultures prior to sepsis, for anatomic sites cultured, or for pathogens recovered. We conclude that surface cultures are of limited value in predicting the etiology of sepsis in neonates.

Algorithms

Comparison of the bactericidal activity of ciprofloxacin alone and in combination with selected antipseudomonal beta-lactam agents against clinical isolates of Pseudomonas aeruginosa.

The bactericidal activity of ciprofloxacin against 60 clinical isolates of Pseudomonas aeruginosa was evaluated by exposing replicating microorganisms to concentrations ranging from 0.12 to 2 micrograms/ml for 48 hr. In addition, ciprofloxacin was combined with selected antipseudomonal beta-lactams using subinhibitory concentrations (1/4 x MIC, 1/2 x MIC) of each. We found that a concentration of 2 micrograms/ml of ciprofloxacin resulted in bactericidal activity (greater than or equal to 99.9% killing of the final inoculum) at 8 and 12 hr for the highest percentage of isolates (95 and 96.7%, respectively). At the breakpoint concentration (1 micrograms/ml), there was bactericidal activity against 81.7% of these isolates at 8 hr and 78.7% at 12 hr. By 24 and 48 hr, regrowth was frequently seen for concentrations of 1 and 2 micrograms/m (76.7 and 41.7%, respectively). This regrowth represented limited progression of resistance (4- to 16-fold increase in MICs) to ciprofloxacin without cross-resistance to other classes of antibiotics. The combinations containing ciprofloxacin and beta-lactam agent were synergistic for isolates that were susceptible to both agents. Moreover, the combinations prevented the emergence of resistance to either drug.

Anti-Bacterial Agents

The problem of selecting antimicrobial agents before (or without) the results of susceptibility testing.

The appropriate selection of an antimicrobial regimen depends upon more factors than merely the results of susceptibility testing. It is a task more difficult today because of the recent development of many new antimicrobial agents. Clinicians who prescribe antibiotics need to invest time and energy beyond reading a package insert in order to gain familiarity with antimicrobial agents. Understanding the antimicrobial and pharmacologic properties of a few agents from each class of antimicrobial agents will help make the selection of empiric regimens less difficult. Essential to empiric therapy is frequent and habitual reassessment of antimicrobial regimens with possible application of cost-effective modifications kept in mind. Once the pathogen is isolated, the empiric regimen can be modified. The very last factor that is used in modification of the antimicrobial regimen is the result of susceptibility testing. Prior to (or without) this information, the clinical outcome of serious infections most often will depend upon the early institution of appropriate empiric therapy.

Anti-Infective Agents